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The 1,3/1,6 form of beta glucan is used in several branded formulae, even prescription products. Derived from mushrooms and increasingly also nutritional yeast sometimes marine algae. Turkey tail mushroom extract has a standalone entry. Beta glucans have a vast amount to research showing how they can help stimulate and balance a healty immune response.
Analysis across several trials reports shiitake mushroom based lentinan with chemotherapy reduces progression risks up to a third in digestive cancers. Results are equivalent for oral supplementation of lentinan as for injectable forms, when both have been tested. Glucans can be taken in substantial amounts too, with good absorption. Digestive tract cancers such as colorectal and gastric have the most research, but there are additional studies in lung cancer, melanoma, even recently with CD40 inhibitors for pancreatic cancer. Often the effects are relatively stronger during more advanced stages.
Many of the most damaging oncology drug side effects can be reduced, frequently halved. This is due to the protective actions of glucans on immune system cells, seen in markers like white blood cell count. Reports vary from a few percent to a 50% effect in patients, of course depending on the oncology drugs and regime needed. Branded pharma grade products such as odetiglucan (Imprime PGG) are reported to improve outcomes in immunotherapy. Both directly, by enhancing the immune system response the tumor itself and reducing resistance, and also indirectly by limiting damaging side effects. And, almost halving the progression of triple negative breast cancers treated with pembrolizumab (Keytruda), look into the Examples below. Trials are ongoing for improving lung, colorectal, Non-Hodgkin lymphoma and breast cancer therapy already. Nichi-glucan are also yeast derived refined glucan, available from Japan https://gncorporation.com/en/shop-top-en/ , with strong evidence for improved immune system health.
High grade commercially available products derived from yeast including Saccharomyces cerevisiae include those based on Wellmune such sa California Gold Immune Defense, or Yestimun, such as Biogens. And brands such as Immiflex and others. There are also branded refined mushroom based products such AHCC from shiitake, which has recent positive trials in clearing HPV infections that drive cervical cancer recurrence. Also improving outcomes in liver cancer including better quality of life during chemotherapy (see References). There is abundant evidence in clinical studies alongside oncology drugs for improving blood markers, immune health and quality of life. Start a regular dose to help limit immune inflammatory response before oncology therapies and consider higher doses if needed once treatments start.
Glucans from processed oats are distinctly different, and are FDA approved for their cholesterol reduction. Excess cholesterol is linked to progression. These help improve microbiome health which can be a crucial factor in outcomes (see Pathfinder examples)
In total 650 IPD from 5 trials were available. Lentinan significantly prolonged the overall survival… The overall hazard ratio (HR) was 0.80 and there was no heterogeneity between trials. Additionally, lentinan was possibly more effective in patients with lymph-node metastasis than in non-node metastasis patients… The addition of lentinan to standard chemotherapy offers a significant advantage over chemotherapy alone in terms of survival for patients with advanced gastric cancer.<...
In our meta-analysis, 12 clinical studies of lentinan injection combined chemotherapy in the treatment of NSCLC [lung cancer] were finally included in this meta-analysis. The pooled results indicated that the objective response rate was significantly improved in the lentinan injection combined chemotherapy group compared with chemotherapy group only (RR = 1.31). The chemotherapy-related toxicity of III/IV gastrointestinal reaction (RR = 0.54) and III/IVgranulocytopenia (RR = 0.65) were signif...
Confirmed response was also evident in patient with liver or visceral metastases, high LDH. 10 IMPRIME 1 pts were originally ER/PR+, received hormonal Tx and progressed to TNBC. Of these, 5 are confirmed PR, 4 SD (3 still on Tx), 1 PD. No unexpected safety signals observed. Conclusions: These are the first clinical data to suggest that PGG provides added clinical benefit for pts with previously treated mTNBC and support further development of PGG + P for mTNBC
β-glucan combined with Envafolimab (an anti-PD-L1 antibody) and Endostar (an angiogenesis inhibitor) has considerable efficacy and safety for immune rechallenge in metastatic NSCLC [lung cancer] patients who failed of anti-PD-1 treatment previously, especially for PD-L1 positive patients…As a “chemo-free” treatment regimen, attempting to regulate the TME for the purpose of immune rechallenge, this is more acceptable for cancer patients.
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| https://ar.iiarjournals.org/content/29/7/2739 | 5 | Lentinan significantly prolonged the overall survival (stratified log-rank p=0.011). The overall hazard ratio (HR) was 0.80 (95% confidence interval=0.68-0.95) and there was no heterogeneity between trials. Additionally, lentinan was possibly more effective in patients with lymph-node metastasis than in non-node metastasis patients (P for interaction=0.077). Conclusion: The addition of lentinan to standard chemotherapy offers a significant advantage over chemotherapy alone in terms of survival for patients with advanced gastric cancer | The combination of chemotherapy based on mainly fluorinated pyrimidines and lentinan statistically significantly prolonged the overall survival (stratified log-rank p-value=0.011). The overall HR was 0.80 (95% CI=0.68-0.95) and there was no heterogeneity between trials (heterogeneity p-value=0.466, Figure 3). The HR adjusted by trial and nine baseline characteristics (age, sex, performance status (≥2 or not), recurrent, prior therapy, surgery, peritoneal metastasis, hepatic metastasis, lymph-node metastasis) was 0.76 |  |
| https://hibercell.com/wp-content/uploads/2020/12/uhlik-et-al-sabcs-poster-final-112719.pdf | 5 | Data presented here are from a primary analysis when all patients have been enrolled and through at least 12 weeks on therapy (2 CT scans/tumor assessments). In the intent-to-treat population (N=44; median duration of follow-up of 19.1 months..), confirmed ORR was 15.9% (1 CR, 6 PRs). Stable disease (SD) >12 wks as best response was observed in nearly 40% of pts (17/44). Four of these 17 were stable for≥24 wks. OS at 1 year are 57.6% with median OS currently at 16.4 months ... A majority of pts (62.5%) showed target lesion (TL) reduction or stabilization | The combination of Imprime and pembro showed promising response rates and overall survival in chemo- refractory metastatic TNBC. Biopsy analyses consistently revealed activation of both myeloid and T cells with extensive infiltration into tumor tissue. Examination of response patterns and clinical benefit revealed extended OS even in pts not classified as responders by RECIST. Indeed, extended OS was most evident in pts with any reduction in TL, regardless of NL/NTLs |  |
| https://jitc.bmj.com/content/8/Suppl_1/A10.1 | 4.5 | Enhanced OS was observed in patients with >1.3 fold increase in CH50 (8/19; HR 0.385; p=0.1) or >1.5-fold reduction in the frequency of exhausted CD8 T cells (8/19; HR 0.102; p=0.001). The IPD responses observed in the ITT population included formation of circulating immune complexes (peak levels ranging from ~4.5-16.1-fold) and production of complement activation protein SC5b9 (~3.4-25.6-fold), and increase in the frequency of HLA-DR+ myeloid cells (~0.43-3.71-fold). Conclusions Overall, these data, albeit in a small population, demonstrate that Imprime/pembro combination can drive the innate/adaptive IPD responses that are critical for providing clinical benefit to the patients who have progressed through prior CPI treatments. | the disease control rate was 45% (1 CR and 8 SD), 6-month and 12-month OS rates were 65% and 45% respectively, and median OS (mOS) was 8.8 months. In the patients showing disease control, a significant increase in CH50, the classical pathway complement function (~0.7-2.6-fold), HLA-DR expression on classical monocytes (~0.61-1.94-fold) and reduction of frequency of PD-1+Tbet-EOMES+ exhausted CD8 T cells (~0.9-4-fold) was observed. Stimulation of peripheral blood mononuclear cells from a subset of patients by CD3/CD28 beads showed enhanced production of IL-2 and IFN-gamma in the CD8 T cells. Some of these IPD responses were also associated with 6-month landmark OS analyses. Additionally, whole blood gene expression analyses showed >2-fold upregulation of several myeloid and T cell activation genes | |
| https://journals.lww.com/indianjcancer/fulltext/2015/52001/a_meta_analysis_of_lentinan_injection_combined.7.aspx | 4.5 | Lentinan injection combined chemotherapy significant increase the objective response rate and decreased the chemotherapy-related toxicity....the objective response rate was significant improved in the lentinan injection combined chemotherapy group compared with chemotherapy group only (relative risk [RR] = 1.31). The chemotherapy-related toxicity of III/IV gastrointestinal reaction (RR = 0.54) and III/IV granulocytopenia (RR = 0.65) | Twelve studies reported the treatment objective response rate. The pooled results indicated that the objective response rate was significantly improved in the lentinan injection combined chemotherapy group compared with chemotherapy group only (RR = 1.31, 95% CI: 1.14–1.52). For subgroup analysis, the NP chemotherapy combined with lentinan injection does not improve the objective response rate (RR = 1.14, 95% CI: 1.14–1.52, P > 0.05); but the objective response rate can be significantly improved by GP or TP combined with lentinan injection with RR of 1.39 | |
| https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5418307/ | 4 | Compared to control treatment, the addition of BTH1677 numerically increased ORR [overall response rate] by both investigator (47.8% vs 23.1%) and central (36.6% vs 23.1%; ) .. BTH1677 [beta glucan derived] was well tolerated..Biomarker-positive patients displayed better ORR [overall response rate ] and OS [overall survivial] than negative patients. Conclusions BTH1677 combined with cetuximab/carboplatin/paclitaxel was well tolerated and improved ORR as first-line treatment in patients with advanced NSCLC. Future patient selection by biomarker status may further improve efficacy | BTH1677 in combination with cetuximab and concomitant carboplatin and paclitaxel improved ORR and was well tolerated in patients with previously untreated, advanced NSCLC. At the time this study was initiated, cetuximab was undergoing regulatory review for first-line use in late-stage NSCLC patients, but ultimately never received approval. Hence, although the treatment regimen used here will not proceed to further evaluation, the results of this study support the concept of improved efficacy with the addition of BTH1677 to antibody therapy. | |
| https://jeccr.biomedcentral.com/articles/10.1186/1756-9966-27-40 | 4 | In this study, twenty patients with advanced malignancies receiving chemotherapy were given a β-(1,3)/(1,6) D-glucan preparation (MacroForce plus IP6, ImmuDyne, Inc.) and monitored for tolerability and effect on hematopoiesis. Our results lead us to conclude that β-glucan is well-tolerated in cancer patients receiving chemotherapy, may have a beneficial effect on hematopoiesis in these patients and should be studied further, especially in patients with chronic lymphocytic leukemia and lymphoma. | None of the twenty patients reported any new symptoms while taking the β-glucan. Sixty per cent of the patients reported a sense of well-being while taking the β-glucan and asked to remain on the treatment even after the completion of the study. Forty per cent of the patients who experienced fatigue during their chemotherapy treatments prior to entering the study reported feeling less fatigued while taking the β-glucan. In addition, one patient with lymphoma and significant cervical adenopathy who delayed his standard chemotherapy for 4 weeks during the study and only took the β-glucan, noted a marked reduction in the size of the nodes while taking the β-glucan alone. | |
| https://bmcimmunol.biomedcentral.com/articles/10.1186/s12865-024-00651-x | 4 | β-glucan combined with Envafolimab and Endostar has considerable efficacy and safety for immune rechallenge in metastatic NSCLC patients who failed of anti-PD-1 treatment previously, especially for PD-L1 positive patients. | . The overall response rate (ORR) was 21.7% and disease control rate (DCR) was 73.9%. Median progression-free survival (mPFS) and median overall survival (mOS) was 4.3 months [95% CI: 2.0–6.6] and 9.8 months, respectively. The mPFS between PD-L1 positive and negative subgroup has significant difference (6.3 months vs. 2.3 months) | |
| https://link.springer.com/article/10.1007/s12325-008-0079-x | 4 | Combination therapy involving lentinan, RFA [radiation] and TACE [chem0] was beneficial in terms of increasing mean survival duration, tumour necrosis and reducing the recurrence rate. Lentinan may therefore be of benefit to HCC patients. | The tumour recurrence rate was significantly lower in the combination group (17.8%), compared to the TACE group (45.8%), the RFA group (34.7%) and the TACE/RFA group (29.0%; P<0.05). Finally, mean survival duration was significantly higher in the combination group (28.2 months; P<0.05). | |
| https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10763102/ | 4 | The existing clinical studies have revealed the application effect of LNT in colorectal cancer.Chen et al. randomized controlled experiments found that LNT combined with chemotherapy regimen can greatly improve the effective rate (chemotherapy regimen with 28% effective rate, LNT combined with effective rate 52%) in colorectal cancer [63]. Moreover, Tu et al. also found that LNT combined with pentafluorouracil can not only enhance the immune function of colorectal cancer patients (CD4/CD8 ratio is elevated), but also significantly improve the quality of life of patients | The clinical effect of LNT in gastric cancer has been widely reported. A randomized controlled study in Japan showed that LNT combined with pentafluorouracil improved survival time for advanced gastric cancer, which is consistent with the results of a meta-study of five randomized controlled trials [78, 79]. | |
| https://pmc.ncbi.nlm.nih.gov/articles/PMC10252021/ | 4 | New strategies are currently under investigation. The IMPRIME-1 trial tested the efficacy of Imprime-PGG, an innate-immune activator, in combination with pembrolizumab for heavily pretreated metastatic TNBC patients. The trial showed an ORR of 15.9%, a DCR of 54.5%, and a median OS of 16.4 months, compared to 9 months for those receiving pembrolizumab alone | Imprime PGG (Imprime), an intravenously-administered, soluble β-glucan, has shown compelling efficacy in multiple phase 2 clinical trials with tumor targeting or anti-angiogenic antibodies. Mechanistically, Imprime acts as pathogen-associated molecular pattern (PAMP) directly activating innate immune effector cells, triggering a coordinated anti-cancer immune response. Herein, using whole blood from healthy human subjects, we show that Imprime-induced anti-cancer functionality is dependent on immune complex formation with naturally-occurring, anti-β glucan antibodies | |
| https://www.tandfonline.com/doi/full/10.2217/crc-2016-0010 | 4 | In summary, BTH1677 [Imprime yeast based beta glucan] immunotherapy appears to be well tolerated and demonstrates promising evidence of efficacy when used in combination with cetuximab, with or without irinotecan, in patients with advanced mCRC. Randomized controlled studies further exploring dose-response evaluations and incorporating more current standard-of-care treatment paradigms in patients with expanded RAS wild-type tumors would be needed to further explore the clinical benefit of BTH1677 in mCRC | In KRAS wild-type patients in group 1, the ORR, DCR and TTP of 42.9%, 100% and 5.2 months were similar to published results for KRAS wild-type patients treated with cetuximab/irinotecan (ORR: 32.4–43.6%; DCR: 70.2–76.9%; TTP: 5.5 months) [Citation38,Citation39], while in group 2, the ORR, DCR and TTP of 45.5%, 81.8% and 5.5 months were slightly higher than published results for these parameters in KRAS wild-type [i.e non gene mutated] patients undergoing cetuximab monotherapy (ORR: 13–28%; DCR: 48.0–78.0%; TTP: 1.4–3.7 months) | |
| https://pmc.ncbi.nlm.nih.gov/articles/PMC11381272/ | 4 | Patients in the current our study demonstrated an mPFS of 10.4 (95% CI, 9.52-11.27) months, surpassing the mPFS of 7.7 reported in the CheckMate-649 study (24). Another phase III clinical study (the Orient-16 study) demonstrated that patients with a PD-L1 CPS >5 had an mPFS of 7.7 months, compared to only 7.1 months for the entire study population, with an ORR of 58.2% (25). These findings suggest potential advantages of the β-glucan plus immunotherapy plus chemotherapy over these other therapies for advanced GC | These preliminary results suggest that in patients with advanced GC, even those with poor ECOG performance, β-glucan combined with camrelizumab and SOX chemotherapy offers considerable clinical benefits and a manageable safety profile. Additional studies including control groups and larger patient populations are needed to further explore these initial findings. | |
| https://pubmed.ncbi.nlm.nih.gov/10522061/ | 4 | Median survival was significantly longer in the lentinan group than in the control group (297 days vs. 199 days, p = 0.028). One-year survival rate was greater in the lentinan group than in the control group (49.1% vs. 0%). Total QOL score, especially appetite and sleep quality, was significantly improved with the administration of lentinan. | Lentinan is considered to prolong survival and improved quality of life when gastric cancer patients with unresectable or recurrent diseases are treated in combination with other chemotherapeutic agents. | |
| https://www.mdpi.com/2504-3900/79/1/1 | 4 | 8 meta-analyses met inclusion criteria. Retrieved evidence reported that lentinan may be useful to improve response rate, 1-year survival, performance status, quality of life and radio/chemotherapy toxicity when administered in adjunct to standard therapy, especially for some lung and gastrointestinal cancers. | In particular, lentinan integrative therapy was able to ameliorate performance status and radio/chemotherapy toxicity in patients with esophageal, gastric and colorectal cancer, whereas it was capable of improving response rate and adverse effects of standard therapy in subjects with lung malignancies. Individuals with advanced-stage solid tumors also benefited from lentinan integrative supplementation in terms of 1-year survival rate and health-related quality of life. | |
| https://www.sciencedirect.com/science/article/pii/S0899900725001297 | 4 | Among the 22 patients who completed the study, the Nichi BRITE group showed notable increases in BG-IgA (+109.09%), CD209 (+54.68%, p=0.034), and SAA (+800.70%, p=0.050), while CA 19-9 decreased significantly (-5.86 U/ml, p<0.001). Decrease in CD44 levels was greater in Nichi BRITE (-35.51%) than in Placebo group (-14.05%). Disease-free survival (DFS) was longer in the Nichi BRITE group (16.1 months) compared to the Placebo group (12.4 months), with a lower recurrence rate (50% vs. 71.4%) for pancreatic cancers. | . Notably, patients in the Nichi BRITE group demonstrated prolonged survival despite recurrence, with some cases of lung and residual pancreatic recurrence still surviving, suggesting a potential immune-modulating effect contributing to tumor control and extended survival outcomes (...Administration of Nichi BRITE β-glucan during the perioperative period in patients undergoing surgery for pancreatic, bile duct and duodenal malignancies has been safe, and it has yielded immune enhancement and improvement in biomarkers of better prognosis. Reduction in circulating cancer stem cells and pancreatic cancer marker CA19-9 make us recommend this Nichi BRITE β-glucan be included in onco-nutrition guidelines for patients undergoing surgical removal of malignant tumours. | |
| https://aacrjournals.org/cancerres/article/84/17_Supplement_2/PR-10/747743/Abstract-PR-10-Phase-1b-study-of-maintenance | 4 | Two patients remained on treatment for >100 days. The pharmacodynamic profile was consistent with the mode of action of odetiglucan and CDX-1140, including a reduction in peripheral Dectin-1 expressing monocytes and transient decreases in peripheral B cells. Patients with disease control (PR or SD, n=2) compared to patients with progression (PD, n=2) showed expansion of peripheral Ki67+ CD8+ T cells following treatment. Analysis of a paired tumor biopsy from 1 patient with PD confirmed penetration of odetiglucan into a liver metastasis with expansion of CD11b+ macrophages and a reduction of cytokeratin+ tumor content, but without significant changes in T cell infiltration | The combination of odetiglucan and CDX-1140 was feasible and safe when administered as maintenance therapy in patients with mPDAC whose disease had not progressed on 1L chemotherapy. Treatment produced encouraging activity with changes in immunological correlates associated with disease control. These early results support further investigation combining odetiglucan with a CD40 agonist in mPDAC. | |
| https://pubmed.ncbi.nlm.nih.gov/19579616/ | 4 | A superfine dispersed lentinan-containing supplementary food is effective for hepatocellular carcinoma patients' survival. Long-time ingestion is preferable. Assessment of lentinan-binding CD14+ monocytes is a promising prognostic predictor | Thirty-six patients were eligible among 40 enrolled patients. Median survival time of eligible patients was 13.6 months (95% confidence interval, 8.7-18.9 months). Survival times of patients who ingested test food for a mean period of 47 weeks (range, 26 to 145 weeks) were significantly longer than that of patients who ingested for 7 to 12 weeks | |
| https://acsjournals.onlinelibrary.wiley.com/doi/full/10.1002/cncr.29421 | 4 | Thirty-six patients were treated; no DLTs were encountered. The overall PSA response rate was 11%. Two patients receiving 8 and 14 g/d demonstrated complete response (CR): their PSA declined to undetectable levels that continued for 49 and 30 months. Two patients who received 8 and 12 g/d experienced partial response (PR). After 3 months of therapy, 13 (36%) patients experienced some PSA decrease below baseline. Patients with CR and PR demonstrated higher levels of baseline interleukin-15 than nonresponders; for this group, we observed therapy-associated declines in MDSCs. | Importantly, in 2 patients, PSA decreased to undetectable levels after WBM treatment. To the best of our knowledge, this has not been observed in other studies examining phytochemical compounds for biochemically recurrent prostate cancer. Almost all of the patients in our study (92%), including 2 patients with CR, had received prostatectomy and radiation therapy. As such, patients had exhausted a chance for a cure via traditional localized treatment. Compliance with the daily ingestion of up to 28 large mushroom powder tablets was excellent, reflecting a lack of significant, chronic toxicity. The most common adverse events were grade 1 abdominal bloating and grade 1 SGPT/SGOT elevation. One patient sustained asymptomatic grade 3 hyponatremia. | |
| https://ascopubs.org/doi/10.1200/JCO.2024.42.23_suppl.96 | 4 | Administration of Nichi BRITE glucans to patients undergoing surgical resection of malignant pancreatic tumor was safe and it enhanced biomarkers of innate and adaptive immunity. Nichi BRITE significantly decreased the circulating cancer stem cell marker sCD44 implying a lesser recurrence risk, especially in patients with high NLR ratio who have a poor prognosis, and significantly reduced the CA 19-9 levels implying a better prognosis, making us recommend it as an adjuvant to patients undergoing surgeries | Decreased sCD44 when correlated against Neutrophil to Lymphocyte Ratio (NLR), a significant positive correlation was in “G” (r statistic= 0.758; p-value =0.006; 95% CI= 0.2907~0.9335), but a negative correlation in “P”. Pancreatic cancer marker CA19-9 decreased significantly in three months follow up in “G” (-86.02 U/ml) whereas it increased in “P” by +5.91 U/ml. Mean survival of Nichi BRITE group was 25.9 months against 22.3 months in “P” grou | |
| https://www.tandfonline.com/doi/full/10.1080/14712598.2018.1523392 | 3.5 | Beta-glucans, when present in food and following uptake in the proximal gut, stimulate immune cells present in gut-associated lymphoid tissue and initiate highly conserved pro-inflammatory pathways. When tested in mouse cancer models, β-glucans result in better control of tumor growth and shift the TME toward a T cell-sensitive environment. Along these lines, we advocate that intake of β-glucans provides an accessible and immune-potentiating adjuvant when combined with adoptive T-cell treatments of cancer. | a study by Cosola and colleagues reported a decrease in p-cresyl sulfate levels in urine and an increase in short chain fatty acid levels in feces upon oral administration of a β-glucan derived from H. vulgare, suggesting a saccharolytic shift in gut microbiota metabolism [Citation82]. Zitvogel and colleagues demonstrated a dominance of distinct commensal species in patients who showed a clinical response toward PD-1 checkpoint inhibitors, making the observed effect of β-glucans on the microbiome highly relevant in the context of T cell therapies | |
| https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6695648/ | 3.5 | An extremely impactful aspect of β-glucan treatment is that it has been demonstrated to modulate the TME. Additionally, β-glucan is safe to use, non-immunogenic, and thus incites no other non-specific responses. It is well-tolerated even with a dose up to 10 mg/kg, induces specific responses through specific receptors and contains many side groups that allow further modification. These features establish β-glucan as a potent adjuvant [55]. Use of adjuvants not only with prophylactic vaccines, but also in therapeutic formulations or alone for immunomodulatory functions have been gaining popularity recently. Fungal β-glucan has been used as an adjuvant, along with other formulations, in both cancer prophylaxis and therapy, and as a single agent for immunomodulatory purposes, and are therefore referred to as immunoadjuvants | Modulation of the TME from an immune-suppressive to an inflammatory environment thus has a very promising potential as an anti-cancer therapy [55]. Fungal β-glucans have the potential to effectively manipulate the TME by influencing both innate and adaptive immune responses [56]. Once innate cells are activated through β-glucan binding to PRRs, as described above, they are recruited to further educate and activate adaptive immune cells. Fungal β-glucans thus have the ability to bridge the innate and adaptive immune responses | |
| https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2022.887457/full | 3.5 | In summary, we found that the immune adjuvant WGP β-glucan improved the infiltration of both DCs and macrophages in the TME, while PD-1/PD-L1–blocking antibodies promoted the balance of T cells to antitumor effectors. Furthermore, combination therapy with WGP β-glucan plus PD-1/PD-L1–blocking antibodies was found to improve mPFS in ICB-resistant patients with advanced cancer. These results suggest that WGP β-glucan is a potentially useful adjuvant in combination with various ICB therapies in clinical practice. | ICB-resistant patients who were treated with β-glucan plus PD-1/PD-L1–blocking antibodies demonstrated a mPFS of 3.67 and a mOS of 8.0 months. These results suggest that β-glucan has promise in reversing resistance to immunotherapy in patients with advanced cancer. Furthermore, no significant toxicities were observed among study patients treated with β-glucan. Furthermore, compared with rechallenge of ICB therapy (Fujita et al., 2018; Niki et al., 2018), add or replace with different classes of ICB ...the combination therapy with WGP β-glucan is efficacy and practicability for patients. |  |
| https://www.mdpi.com/1422-0067/20/15/3618 | 3.5 | Though fungal β-glucan’s have been studied and used as an immune-stimulant for centuries, there are many aspects of β-glucan biology that are only now being brought to light which are profoundly shaping immunological paradigms. Specifically, the ability of β-glucan to incite the metabolic reprograming and epigenetic regulation of myeloid cells and macrophages is a revelation in the fields of both infectious disease and cancer. As the concept of trained immunity in the context of metabolic reprograming is relatively novel and unstudied, we expect there to be a great deal of interest going forward in how innate memory responses may play a role in cancer immunoprevention and treatmen | An extremely impactful aspect of β-glucan treatment is that it has been demonstrated to modulate the TME. Additionally, β-glucan is safe to use, non-immunogenic, and thus incites no other non-specific responses. It is well-tolerated even with a dose up to 10 mg/kg, induces specific responses through specific receptors and contains many side groups that allow further modification. These features establish β-glucan as a potent adjuvant [55]. Use of adjuvants not only with prophylactic vaccines, but also in therapeutic formulations or alone for immunomodulatory functions have been gaining popularity recently. Fungal β-glucan has been used as an adjuvant, along with other formulations, in both cancer prophylaxis and therapy, and as a single agent for immunomodulatory purposes, and are therefore referred to as immunoadjuvants [ | |
| https://pubmed.ncbi.nlm.nih.gov/12076865/ | 3.5 | Of the 269 patients, 113 received AHCC orally after undergoing curative surgery (AHCC group). The AHCC group had a significantly longer no recurrence period (hazard ratio (HR), 0.639) and an increased overall survival rate (HR, 0.421) when compared to the control group by Cox's multivariate analysis. | Active hexose correlated compound (AHCC) is a newly developed functional food. In vitro experiments have shown that AHCC enhances natural killer cell activity, and may be considered a potent biological response modifier in the treatment of cancer patients. However, the effects of AHCC in a clinical setting have not been reported. We seek to determine whether AHCC can improve the prognosis of hepatocellular carcinoma (HCC) patients following surgical treatment. | |
| https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3661165/ | 3.5 | We have shown that the combination of 3F8 [Chemo] and BG is safe. The encouraging responses observed in a heavily pretreated population support further (Phase II) studies of BG combined to other immunomodulatory agents for the therapy of NB and other tumors amenable to CR3-mediated immunotherapy. Given the low toxicity of BG and the absence of any evidence of dose-response correlations, we recommend a dose of 40–80 mg/Kg/day for future trials. | Objective responses were documented in 63% (15/24) of patients. All patients had previously received multiple chemotherapy regimens (median 3; range 2–6). Most patients had poor BM reserve (12/24 patients had platelet count < 100,000/μL at baseline) and would have been ineligible for most Phase I/II clinical studies involving conventional chemotherapeutics. Anti-NB responses were recorded for BM disease (histology, MIBG scans) and biochemical markers (urine catecholamines), but, as reported in other mAb-based clinical trials, responses in soft tissue disease were rare. In general, responses were transient and modest. Near-to-complete resolution of extensive MIBG-avid metastases after one cycle of 3F8 plus BG was observed in two chemorefractory patients | |
| https://www.mdpi.com/1422-0067/20/15/3618 | 3.5 | An extremely impactful aspect of β-glucan treatment is that it has been demonstrated to modulate the TME. Additionally, β-glucan is safe to use, non-immunogenic, and thus incites no other non-specific responses. It is well-tolerated even with a dose up to 10 mg/kg, induces specific responses through specific receptors and contains many side groups that allow further modification. These features establish β-glucan as a potent adjuvant [55]. Use of adjuvants not only with prophylactic vaccines, but also in therapeutic formulations or alone for immunomodulatory functions have been gaining popularity recently. Fungal β-glucan has been used as an adjuvant, along with other formulations, in both cancer prophylaxis and therapy, and as a single agent for immunomodulatory purposes, and are therefore referred to as immunoadjuvants | Though fungal β-glucan’s have been studied and used as an immune-stimulant for centuries, there are many aspects of β-glucan biology that are only now being brought to light which are profoundly shaping immunological paradigms. Specifically, the ability of β-glucan to incite the metabolic reprograming and epigenetic regulation of myeloid cells and macrophages is a revelation in the fields of both infectious disease and cancer. As the concept of trained immunity in the context of metabolic reprograming is relatively novel and unstudied, we expect there to be a great deal of interest going forward in how innate memory responses may play a role in cancer immunoprevention and treatment. | |
| https://pmc.ncbi.nlm.nih.gov/articles/PMC11294916/ | 3.5 | β-Glucan, as an immunomodulator, has demonstrated promising anti-tumor effects in preclinical studies of colorectal cancer, pancreatic cancer, and gastric cancer (14, 24, 25). Notably, the high stability of β-glucan renders it a crucial component for serving as a carrier for targeted drugs against gastric cancer (17). In clinical studies, β-glucan has been shown to improve the 5-year survival rate of hepatocellular carcinoma, gastric cancer, and colorectal cancer, while reducing the recurrence rate (26–28). Additionally, it can mitigate adverse reactions caused by chemotherapy, such as nausea, abdominal pain, mucositis, diarrhea, and leukopenia/thrombocytopenia | Lentinan, a β-glucan extracted from mushrooms, has been proven to possess antitumor activity (25, 85). Researchers have confirmed its preventive and therapeutic effects on gastric cancer, and the mechanisms of its action include: 1) inhibiting the G2/M phase of the gastric cancer cell division cycle to exert anti-proliferative effects; 2) Lentinan can attenuate the wound healing, colony formation, and migration abilities of AGS cells; 3) Lentinan can increase the expression of phospho-p38, while reducing the expression of phospho-ERK1/2 and Mu-2-related death-inducing gene (MuD) proteins; 4) Lentinan induces the generation of reactive oxygen species (ROS), directly participating in cell death (25). In the treatment of gastric cancer, β-glucan can be used as a main component of drug carriers to jointly exert anti-tumor effects | |
| https://pmc.ncbi.nlm.nih.gov/articles/PMC3191325/ | 3.5 | Our results showed that chemo-immunotherapy using lentinan was superior to chemotherapy alone in terms of survival, although the therapeutic regimens were not completely matched in the 2 treatment groups. The survival time was long in 3 patients in the chemo-immunotherapy group (lung metastasis, 5 years; peritoneal metastases, 5 years and 5 mo; and peritoneal metastases, 6 years and 6 mo after initiation of chemotherapy), while none of the patients in the chemotherapy alone group survived for more than 5 years. The survival rates at 1-, 2- and 5-year were also higher in the group that received lentinan. | Our data on S-1-based chemotherapy showed that the addition of lentinan to chemotherapy prolonged the survival of advanced gastric cancer patients along with immunological activation, compared to chemotherapy alone. Lentinan should be widely accepted for the treatment of unresectable or recurrent advanced gastric cancer. Chemo-immunotherapy combined with lentinan and an S-1-based regimen might be a candidate for the standard treatment of advanced gastric cancer. In Japan, a phase III study comparing therapy with S-1/lentinan with S-1 alone is now underway. | |
| https://pmc.ncbi.nlm.nih.gov/articles/PMC8793419/ | 3.5 | In this study, the 2-year recurrence-free survival rate for resected BCLC-B cases was 48% for those who completed 2 years of treatment and 55.2% for all patients with a history of treatment. These values are better than those previously reported.8,24 The inflammation-based prognostic scores of patients with AHCC, namely LNR, PNI, and SII, were maintained at favorable levels after hepatectomy. AHCC-related toxicity and adverse events were not observed in any patient treated with AHCC. In this study, AHCC has been found to be a promising adjuvant therapy for patients with advanced hepatocellular carcinoma after curative hepatectomy, and this should be verified in randomized trials. | AHCC has been reported to exert immune-protective effects against many types of cancer and the effect of AHCC on the components of the immune system, such as NK cells, dendritic cells (DCs), and T cells, including CD4 and CD8 positive T cells. 15 After AHCC treatment, NK cell activity, which was depressed by an anticancer drug, was reportedly restored and peritoneal macrophage cytotoxicity, nitric oxide production, and cytokine production were stimulated. 12 In patients with breast cancer, who were scheduled to receive postoperative adjuvant anthracycline-based chemotherapy, administration of L. edodes mycelia extract maintained patients’ quality of life and immune function by inhibiting the increase in the proportion of regulatory T cells to peripheral CD4+ cells. 33 Intake of AHCC increased CD8+ T cell lymphocyte levels after 6 cycles of chemotherapy. | |
| https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2024.1424261/full | 3.5 | For patients with advanced gastrointestinal cancer, it is highly desirable to continue chemotherapy with minimal adverse reactions for an extended period. Previous clinical studies have indicated that the adjunctive use of β-glucan during chemotherapy or radiotherapy for hepatocellular carcinoma, gastric cancer, and colorectal cancer can increase the 5-year survival rate by 15% and reduce the recurrence rate by 43% (26–28). In Japan, two types of β-glucans, krestin and lentinan, are licensed as drugs for gastric cancer treatment (85). Among them, Krestin is extracted from Coriolus versicolor, and this preparation has been clinically used for surgical treatment of resectable gastric cancer | Lentinan (LNT) is an immune adjuvant medicine for advanced gastric cancer in Japan, in a multicenter clinical study conducted in Japan, 71 patients with advanced colorectal cancer who met the inclusion criteria were enrolled. In this study, researchers employed superfine dispersed lentinan (SDL), an oral formulation of 1,3-β-glucan, as an adjunctive therapy to assess post-chemotherapy adverse reactions, quality of life (QOL), and the binding capacity of peripheral blood monocytes (PBMs) to lentinan (LNT). After receiving SDL treatment (15 mg/day for 84 days), QOL was significantly improved in the majority of patients. Notably, the PBM binding rate to LNT was significantly higher in the QOL-improved group compared to the non-improved group. | |
| https://onlinelibrary.wiley.com/doi/10.1002/hon.207_2631 | 3 | Rituximab (R) as a single agent is effective in indolent B-NHL (iB-NHL), but response rates and durability fall in relapsed/refractory (r/r) disease. Resistance is in part due to variable complement activation. Imprime PGG (IPGG) is a yeast-derived β-glucan that, when complexed with anti-β-glucan antibodies (ABA) and opsonized by iC3b, activates innate immune cells through CR3. Combining IPGG with R, then, may improve responses in r/r iB-NHL through complement-dependent cytotoxicity | R-IPGG is well tolerated with a promising ORR of 46% in a r/r population. Importantly, treatment with R-IPGG resulted in a cytokine profile that is associated with M1-macrophage polarization and enhanced antigen presentation, and resultant expansion and activation of tumor infiltrating T cells. These IPD responses are not only important for the immune effector mechanisms required for combination with antitumor antibodies, like R, but also for the activity of immune checkpoint inhibitors | |
| https://www.spandidos-publications.com/10.3892/or.2021.8225 | 3 | This approach may aid in the treatment of cancer in specific immunocompromised populations, as it induces a wide variety of biological response modifications. For example, the BRMG application may balance metabolic parameters, including blood glucose and lipid levels, increase peripheral blood cell cytotoxicity against cancer and alleviate chemotherapy-induced side effects in animal models. Thus, the use of a β-glucan vaccine adjuvant approach was suggested for the treatment of cancer via immunoenhancement as a potential strategy for a long-term prophylaxis in immunocompromised individuals or genetically prone to cancer. | The aim of the present review was to provide evidence of a biological response modifier β‑glucan [β‑glucan vaccine adjuvant approach to treating cancer via immune enhancement (B‑VACCIEN)] and its beneficial effects, including vaccine‑adjuvant potential, balancing metabolic parameters (including blood glucose and lipid levels), increasing peripheral blood cell cytotoxicity against cancer and alleviating chemotherapy side effects in animal models. This suggests its value as a potential strategy to provide long‑term prophylaxis in immunocompromised individuals or genetically prone to cancer. | |
| https://www.spandidos-publications.com/10.3892/etm.2010.121/ | 3 | After CM-G [beta glucan preparation] administration, the total leukocyte count increased significantly (p≤0.02), with no associated changes in the lifestyle habits of the patients. A significant increase (p≤0.001) was also observed for red blood cell, hematocrit, hemoglobin and platelet counts. No changes were observed in hepatic or renal function after CM-G administration, and no side effects associated with its use were recorded. These results suggest that using CM-G as an adjuvant to cancer treatment may improve the health parameters of prostate cancer patients | low white blood cell counts were observed prior to CM-G treatment in patients who had received radiation therapy. CM-G has proven effective in stimulating hematopoiesis after repeated doses of radiation, and in increasing granulocytes and other hematopoietic indices (18). Several experimental models have demonstrated the ability of β-glucans and derivatives administered by different routes to raise blood cell counts after leukopenia caused by cancer treatments | |
| https://pmc.ncbi.nlm.nih.gov/articles/PMC7736624/ | 1 | ..present study demonstrate that LNT [beta-glucan] inhibits the growth of breast tumors in mice and the ability to metastasize to lung tissues, which is accompanied by the decline of HIF-1α in tumor tissues. In vitro, LNT down-regulates hypoxia-induced HIF-1α in a concentration-dependent and Nur77-dependent manner, which is possibly mediated by the ubiquitin proteasome pathway. Our results explain the LNT-mediated mechanism underlying breast tumor suppression, and may provide a theoretical basis for targeting HIFs in the treatment of breast cancer. | In addition to that, the strong association between Nur77 and HIF-1α was also observed in breast cancer specimens. Recently, Nur77 has been proven to be a key immunomodulator and its inhibition may be a promising strategy for cancer immunotherapy [40]. As mentioned above, HIF-1α also participates in the process of tumor immune responses. Given that LNT-mediated HIF-1α inhibition depended on Nur77, it may be inferred that the anti-tumor effect of LNT on breast cancer is through regulating immune response via the Nur77/HIF-1α axis | |
| https://koreascience.or.kr/article/JAKO201429765167366.page | 2.5 | In both groups white blood cell counts decreased after 21 days of the intervention, however in the beta glucan group, WBC was less decreased non significantly than the placebo group. At the end of the study, the change in the serum level of IL-4 in the beta glucan group in comparison with the placebo group was statistically significant (p=0.001). The serum level of IL-12 in the beta glucan group statistically increased (p=0.03) and comparison between two groups at the end of the study was significant | This randomized double-blind placebo-controlled clinical trial was conducted on 30 women with breast carcinoma aged 28-65 years. The eligible participants were randomly assigned to intervention (n=15) or placebo (n=15) groups using a block randomization procedure with matching based on age, course of chemotherapy and menopause status. Patients in the intervention group received two 10-mg capsules of soluble 1-3, 1-6, D-beta glucan daily and the control group receiving placebo during 21 days, the interval between two courses of chemotherapy. White blood cells, neuthrophil, lymphocyte and monocyte counts as well as serum levels of IL-4 and IL-12 were measured | |
| https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4637216/ | 2 | we found that the immune adjuvant WGP β-glucan improved the infiltration of both DCs and macrophages in the TME, while PD-1/PD-L1–blocking antibodies promoted the balance of T cells to antitumor effectors. Furthermore, combination therapy with WGP β-glucan plus PD-1/PD-L1–blocking antibodies was found to improve mPFS in ICB-resistant patients with advanced cancer. These results suggest that WGP β-glucan is a potentially useful adjuvant in combination with various ICB therapies in clinical | Tumor-associated macrophages (TAM) with an M2-like phenotype have been linked to tumor-elicited inflammation, immunosuppression, and resistance to chemotherapies in cancer, thus representing an attractive target for an effective cancer immunotherapy. Here, we demonstrate that particulate yeast-derived β-glucan, a natural polysaccharide compound, converts polarized M2 macrophages or immunosuppressive TAM into an M1-like phenotype with potent immuno-stimulating activity. This process is associated with macrophage metabolic reprograming with enhanced glycolysis, krebs cycle and glutamine utilization | |
| https://www.mdpi.com/2072-6643/12/3/686 | 2 | Beta-glucans reduced mean LDL-Cholesterol (LDL-C) levels from baseline by 12.2%.. after 4 weeks of supplementation and by 15.1%.. after 8 weeks of supplementation. Between baseline and 4 weeks Total Cholesterol (TC) levels showed an average reduction of 6.5% ..in the beta-glucan sequence; while non-HDL-C plasma concentrations decreased by 11.8% ... Moreover, after 8 weeks of beta-glucan supplementation TC was reduced by 8.9% | The observed effect on TC and LDL-C are larger (0.53 and 0.59 mml/L, on average, corresponding to 15.1% and 8.9% of baseline values respectively) than expected, based on the most recent meta-analysis and EFSA opinion, which estimate respectively a mean change in LDL-C of 0.3 mmol/L and 0.21 mmol/L (about 7–10% of baseline concentratios) [7,18]. The reasons of such better performance are not easily explained, but it should be considered the possibility that the tested formulation, to be dissolved in fluids before consumption, might have specific pharmaceutic properties able to enhance the efficacy of the fibers in binding cholesterol and/or its metabolites | |
| https://pmc.ncbi.nlm.nih.gov/articles/PMC11034815/ | 1 | Established pancreatic tumors that were resistant to T cell–targeted immunotherapy could be eradicated by systemic β-glucan in combination with CD40 agonist antibody therapy. The antitumor activity of Dectin-1/CD40 activation required T cells but was independent of classical T cell cytotoxicity and immune checkpoint pathways. Antitumor activity also required IFN-γ and intratumoral macrophages. These results demonstrate that combinatorial targeting of myeloid cell activation pathways can generate strong antitumor immune responses against tumors resistant to conventional immunotherapy | To define the mechanisms and clinical relevance of combinatory myeloid pathway activation, we focused on aCD40 plus BG therapy. At the cellular level, cDC1s, T cells, Ly6C+ monocytes, and CSF1R-dependent TAMs were necessary for maximal therapeutic activity triggered by coactivation of CD40 and Dectin-1, whereas B cells and granulocytes were dispensable. Thus, antitumor activity driven by BG and aCD40 treatment relies on distinct contributions from multiple adaptive and innate leukocyte subsets, which converge to establish a concerted immunological response to cancer |  |
Meta-analysis of gastric cancer clinical trials in Japan looks at the survival advantages along with chemotherapy of 650 patients in 5 clinical trials when combining lentinan, derived from shiitake mushroom. The patient group had non-operable or recurring gastric cancer, many with lymph node metastasis. For patients that received lentinan the fully adjusted relative improved survival overall was 24%, and for those with lymph node metastasis it was higher at 30%. The data for 2 year survival shows nearly 50% more patients from the lentinan group. These results are similar to those obtained from adding immunotherapy drugs to first line chemotherapy, but with reduced side effects.
Reported benefits are somewhat higher in male patients, and those with resected / recurrent gastric cancer. Both AHCC and Lentinex are branded refined supplements likely to achieve similar absorption.
A 2015 meta-analysis compares the improved response rates in non-small cell lung cancers achieved by adding lentinan injections to standard chemotherapies. Oral lentinan has the same effects as injected. 12 studies were analysed, and over 950 patient cases. The aggregated results show a 31% higher response rate to treatment in the patients with lentinan beta glucans taken alongside the oncology treatment. Other reports describe beta glucans ability to reduce tumor resistance mechanisms associated with lower response than expected in both chemotherapy and immunotherapy outcomes.
Also of note, high grade gastrointestinal adverse events were halved, And, granulocytopenia ( associated with weaker immune system) was reduced by a third, meaning lentinan has a good effect both direcly, indirectly and in quality of life.
For metastatic triple negative breast cancers . A 2019 phase II study of yeast derived beta glucans patented product, Imprime also named as odetiglucan. In this case the beta glucan compound is tested with chemotherapy against results published in Keynote086 trials for pembrolizumab immunotherapy used alone.
Odetiglucan with chemotherapy showed about triple the disease control rates, and 50% increased overall survival times. Ogetiglucan continues development in trials. A premium quality off the yeast glucan may well deliver much of benefit, examples are found in the GUIDE
Metastatic spread is frequently linked to immune system inflammatory responses which are increased by cancer to fuel its progression and evade treatment. The so called neutrophil-to-lymphocyte ratio or NLR is a primary biomarker for this. Lowering NLR indicates re-balancing immune system to a less inflammatory state, and improved adaptive vs innate immune response.
Beta glucans often lower NLR and have evidence summarized here for that in other diseases https://www.sciencedirect.com/science/article/pii/S0753332221010271?via%3Dihub And here in relation to research in space travel and how to combat the same inflammatory response in astronauts:
https://pmc.ncbi.nlm.nih.gov/articles/PMC11911466/
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