Turkey Tail Mushroom: Insights From Turkey Tail Cancer Research

TURKEYTAIL MUSHROOM

Polysaccharide K (PSK) is the best known active compound in turkey tail mushroom. In Japanese oncology, PSK is an established supporting compound in several cancers, also under the name Krestin. In China an equivalent PSP extract is used. Along with shiitake based lentinan, these mushroom glucans have a long history of safe use in asian oncology practice deserving of more research. Evidence on turkey tail improving patient outcomes includes more than 40 clinical trials comprising over 180,000 patients with gastric, colorectal, lung, esophageal, and breast cancers, where the PSK extract is used with chemotherapy. Surprisingly positive results can be seen for some, especially in advanced metastatic stage cancers where the risk reductions are similar or even better then some of the most recent oncology drugs on the market. Relative increases in late stage slowing of disease progression can be as much as 45-50% seen in certain cases. Most studies are in advanced gastric and colorectal cancer (see Examples), but research in asia has also shown good effect in lung cancer.

Medicinal mushroom extracts feature frequently in integrative clinical care, and individual case studies with good results exising in clear cell kidney cancer for instance (References). Tumors frequently develop common so called MHC-1 mutations to evade immune system responses, by down-regulating essential molecules needed in immune reactions. These interfere with oncology treatment as well, including immunotherapy especially in late stage metastatic sites. The detailed mechanisms both related to PSK and overall mushroom derived beta glucan content are often connected to restoring and activating these immune responses. A medicinal mushroom extract then, for some cases, can act as a “natural immunotherapy”. Just as with modern drug treatments, the effects can vary and are targeted to specific disease types. MHC-1 down-regulation the most common way cancer evades immunotherapy. And is known to be prominent in colorectal and advanced gastric cancers as well as melanoma. In fact, it is highly implicated especially during progression in most disease including breast and prostate cancer

So mushroom extracts can improve immune system health and lower inflammatory responses used by cancer to evade treatment, but also help microbiome health. Doses of up to 9g daily have been used in clinical trials for supporting immune system restoration after radiotherapy. (see References) As always – seek qualified medical advice on their use. See also Beta Glucans.

TYPICAL ABSORPTION LEVELS

5 – 15%

EXAMPLES OF IMPROVED OUTCOMES

YES

PRE-DIAGNOSIS OR PREVENTION

PENDING

Highlighted Studies

10,617 patients with gastric cancer received gastrectomy and adjuvant chemotherapy. 1295 patients used PSK (PSK group) and 5180 patients never used PSK (control group) were analyzed ..The median overall survival was 6.49 years in the PSK group and 3.59 years in the control group. After adjusting for age, sex, urbanization, income, and comorbidities, adding PSK to adjuvant chemotherapy was the most significant prognostic factor for improved survival Adjuvant chemotherapy combined with PSK si...

Expression-negative [gastric cancer] cases demonstrated 3-year recurrence-free survival (RFS) rates of 65% in the PSK group and 47% in the chemotherapy-only group. Therefore, the PSK group revealed a prolonged survival. For the 82 expression-negative cases with pN2 or greater, the RFS rates were 68% in the PSK group and 28% in the chemotherapy-only group, representing a significant difference. Thus, PSK adjuvant immunochemotherapy may be effective in MHC class I-negative patients, who are in ...

The study showed that oral PSK plus UFT reduced the risk of recurrence by 43.6% in patients with stage II or III, and reduced the overall death rate in patients with pathologic stage III colorectal cancer. In Cox proportional hazard models, the administration of PSK decreased the risk of recurrence and that of lymph node metastasis and a lower primary tumour. After a 5-year follow up, the rate of recurrence was 36.5% with UFT monotherapy and 23.3% with UFT/PSK, with the majority of recurrence...

In all three trials, patients were followed up for at least 5 years after surgery and enrollment of the last patient and outcomes for standard chemotherapy were compared with those for chemotherapy plus PSK…The overall survival risk ratio for all eligible patients was 0.71…and the disease-free survival risk ratio was 0.72 … The results of this meta-analysis suggest that adjuvant immunochemotherapy with PSK can improve both survival and disease-free survival of patients with...

TABLE OF REFERENCES

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https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9302315/	5	The median overall survival was 6.49 years (95% confidence interval in the PSK group and 3.59 years in the control group. The PSK group had a significantly longer survival than the control group. After adjusting for age, sex, urbanization, income, comorbidities and chemotherapy regimen, the use of PSK was still significantly associated with a reduction in the risk	We found a 23% reduction in overall mortality in the resected gastric patients who used PSK in combination with adjuvant chemotherapy after adjusting for confounding factors. According to the regulations of the Taiwan NHI program, indications for adjuvant PSK must be reviewed and approved before it can be prescribed
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3438816/	5	Therefore, the PSK [polysaccharide k from turkey tail] group revealed a prolonged survival. For the 82 expression-negative cases with pN2 or greater, the RFS [recurrence free survivial ] rates were 68% in the PSK group and 28% in the chemotherapy-only group, representing a significant difference. Thus, PSK adjuvant immunochemotherapy may be effective in MHC [immune response marker] class I-negative patients, who are in a state of antitumor immunological tolerance, and patients with advanced lymph node metastasis of pN2 or greater	In conclusion, the present findings indicate that survival-prolonging effects can be expected when PSK is included in the therapy for gastric cancer patients who have undergone curative resection and are at high risk of recurrence due to the presence of lymph node metastasis and the absence of MHC class I expression. PSK can be surmised to exert effects on residual cancer cells that have evaded the anti-tumor immune functions, and also has the potential to prevent lymph node metastasis. However, PSK cannot be expected to be effective in all gastric cancer patients, and identification of biomarkers to identify potential responders is required.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2409633/	5	The study showed that oral PSK plus UFT reduced the risk of recurrence by 43.6% in patients with stage II or III [colorectal cancer], and reduced the overall death rate in patients with pathologic stage III colorectal cancer. In Cox proportional hazard models, the administration of PSK decreased the risk of recurrence and that of lymph node metastasis and a lower primary tumour. After a 5-year follow up, the rate of recurrence was 36.5% with UFT monotherapy and 23.3% with UFT/PSK, with the majority of recurrences being distant metastasis. PSK achieved a 57.5% absolute reduction in recurrence at the 5-year follow-up. The recurrence rate was 34.9–37% for stages II and III, and 33.5–39.3% for stage III with 5-FU/LV and 5-FU/levamisole treatment.. whereas the rates were 49–60% without adjuvant chemotherapy	In our stage III patients, the 4-year disease-free and overall survival rates were 69.1 and 78.2% in the PSK group, as compared with 35.7 and 50% in the controls, respectively. The 5-year disease-free and overall survival rates were 60.0 and 74.6% in the PSK group, as compared with 32.1 and 46.4% in the controls, respectively. A randomised, double-blind study showed that the 5-year disease-free survival for PSK vs placebo was 38 vs 20%, and overall survival for PSK vs placebo was 50 vs 40%, respectively ..Survival with PSK/UFT treatment in pathologic stage III patients was comparable or superior to standard regimens of 5-FU/LV or 5-FU/levamisole..However, survival with UFT monotherapy in pathologic stage III patients was worse, and was similar to that of untreated controls in standard regimen studies
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11030578/	5	However, combining data from the three relevant studies revealed an odds ratio of 0.71 for survival and of 0.72 for disease free survival, so that our meta-analysis indicated a significant improvement in survival as a result of immunochemotherapy with PSK (P=0.006 for survival and 0.003 for disease-free survival). This improvement may be not only statistically but also clinically significant. A reduction of the death rate by 29% and of recurrence by 28% could be substantial and may justify the inconvenience and financial burden of long-term administration of PSK.	While oral fluorinated pyrimidine has already been approved as the standard adjuvant chemotherapy in Japan, an even higher efficacy as a result of the addition of immunopotentiator PSK could open new possibilities for a better therapeutic modality for colorectal cancer. Since PSK, OK-432 and levamisole all have similar immunomodulatory effects, but are not necessarily effective as monotherapy against malignancies, the effect of immunochemotherapy with PSK after curative resection of colorectal cancer may be the result of restoration of immunity in patients who show immunosuppression because of surgery and subsequent chemotherapy. Our previous findings from experimental and human studies also support this concept
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11030720/	5	In conclusion, the results of this meta-analysis suggest that the addition of PSK to standard chemotherapy offers significant advantages in survival over chemotherapy alone for patients with curative resections of gastric cancers. We hope our results will result in a wider acceptance of immunochemotherapy as effective treatment of gastric cancer.	This improvement may well be both statistically and clinically significant. We further conducted a sensitivity analysis using the three trials with the best quality to verify the robustness of our results. The beneficial effect of PSK therapy was confirmed in our sensitivity analysis (HR was 0.78; 95% CI, 0.64–0.97; P = 0.027), which did not yield significantly different results from the larger analysis. We therefore conclude that PSK is effective as adjuvant immunochemotherapy for patients with gastric cancer
https://link.springer.com/article/10.1007/s10147-010-0033-1	5	Twenty-one registered patients with stage III gastric cancer were analyzed. The 3-year overall survival was 62.2% in the PSK group (n = 10) and 12.5% in the control group (n = 11) (P = 0.038). Before operation, there were no significant differences in the proportions of Th1 cells, Th2 cells, Th1/Th2 ratio, CD56(+) T cells, CD57(+) T cells, NK cells, and CD4(+)CD25(+) T cells between PSK and control groups	When all patients were analyzed, patients with increased proportion (>18%) of CD57+ T cells showed worse survival than those with lower (≤18%) CD57+ T cells (3-year survival, 25.0 and 45.7%, respectively; P = 0.046), consistent with our previous report that high CD57+ is an indicator of poor prognosis in patients with advanced gastric cancer. However, in the group treated with PSK + UFT, 3-year survival of CD57-high patients was as great as that of CD57-low patients (66.7 and 51.4%, respectively; P = 0.67).
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10183216/	4.5	Five studies were included in the review that pertained to medicinal mushrooms and gastric cancer. Four of the five studies investigated the effect of the mushroom Turkey Tail (Coriolus versicolor and Trametes versicolor) [28-30] on people with regarding gastric cancer; the fourth study investigated Huaier (Trametes robiniophila murr) a sandy beige mushroom that grows on hardwood trees, and gastric cancer a [31]. Findings from these studies indicated Turkey Tail played a role in prolonging overall survival in gastric cancer patients, with few exceptions	For gastric cancer, Turkey Tail was seen to improve the antitumor immune ability by modulating immune systems, preventing lymph node metastasis, and improving survival outcomes [28-31]. Hauier was also effective in promoting antitumor effects and cell apoptosis in gastric cancer patients [10]. It is important to note, however, that patients in the studies varied regarding cancer stages and chemotherapy treatment types. For example, Polysaccharide K (PSK, the active compound in Turkey Tail) had no effect on the survival outcomes for PD-L1 positive patients but PD-L1 negative patients who received PSK had better survival outcomes than patients who did not receive PSK
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3369477/	4	The phase I data suggest that Tv [turkey tail] is a safe immunotherapy for breast cancer patients that may correct radiotherapy-related immune defects. Based on our findings, Tv mushroom therapy orally administered in the postradiotherapy setting may enhance lymphocyte numbers and NK cell tumoricidal activity. Relapse after primary breast cancer treatment may be related to defects in the innate and adaptive immune system. Research by our center continues to indicate that Trametes versicolor represents a novel immune therapy with significant applications in cancer treatment	Here, we show that RT reduces NK cell activity per NK cell. Higher oral doses of Tv at 6 and 9 grams/day were associated with faster recovery of lymphocytes and NK cell activity, as well as increased numbers of CD8+T cells and CD19+ B cells. There was no evident effect of Tv on the number of CD 16+/56+ NK cells, only on their functional activity. While there is a trend toward higher Tv doses having more pronounced immunological activity, this phase I dose escalation trial was not designed to evaluate dose-dependent changes in immune markers. Preliminary data with these small samples of 3 breast cancer patients per dose cohort group showing dose-related trends lead to the testable hypothesis that 6 grams of Tv may lead to faster immune recovery after radiotherapy
https://www.mdpi.com/2227-9059/10/11/2841	4	Recent research has discovered a small molecule polysaccharide peptide derived from Trametes versicolor that has a distinct structure after decades of Trametes versicolor investigation. Uncertain molecular weight and a complex composition are problems that have been solved through studies on its structure, and it was demonstrated to have strong anti-proliferation activity on colorectal cancer in vitro and in vivo via interaction with EGFR signaling pathway. It opens up new horizons for research in this field, and these low molecular weight polysaccharide peptides provide a new insight of regulation of colorectal cancer proliferation and have great potential as drugs in the treatment of colorectal cancer.	In China, PSK, whose market value was USD 357 million, became a clinically used drug in 1987 [57] after receiving clinical use approval in Japan in 1977. Additionally, earlier studies have indicated that PSK and PSP have potent anti-cancer activities in a variety of cancer situations, including leukemic, breast, cervix, stomach, liver, lung, prostate, ovarian, and colorectal cancer
https://journals.sagepub.com/doi/10.1177/1534735415572883	4	Randomized controlled trials showed benefits on a range of endpoints, including immune parameters and hematological function, performance status and body weight, tumor-related symptoms such as fatigue and anorexia, as well as survival. Although there were conflicting results for impact on some of the tumor-related symptoms and median survival, overall most randomized controlled trials supported a positive impact for PSK on these endpoints. PSK was safely administered following and in conjunction with standard radiation and chemotherapy. Conclusions. PSK may improve immune function, reduce tumor-associated symptoms, and extend survival in lung cancer patients. Larger, more rigorous randomized controlled trials for PSK in lung cancer patients are warranted.	All five studies used measures of survival as endpoints. Significantly increased median survival was reported with use of PSK among stage 0 to 1 non–small cell lung cancer patients who had responded to radiation 16, 17; in patients receiving PSK, OK-432, or both as immunotherapy in addition to chemotherapy or radiation therapy.23 One study found no difference between treatment with immunotherapy (PSK, OK-432, or Tegafur) plus chemotherapy compared to chemotherapy alone,22 and one study reported increased median survival associated with use of PSK but did not provide a measure of significance for the finding
https://www.hilarispublisher.com/open-access/renal-cell-carcinoma-a-case-series-with-integrative-treatment-2329-6771-S1-002.pdf	3.5	Beneficial effects of integrative care were observed in this case series. Disease progression and symptoms related to adjuvant treatment were significantly decreased in these patients after integrative supportive care was initiated and effects persisted through the final observation period. Further controlled studies are needed among larger groups of patients to determine the clinical efficacy of medicinal mushrooms and integrative oncology in the treatment of RCC	The pathophysiology of RCC and the mechanisms of intrinsic and acquired resistance to therapy are complex. A reductionist approach to therapy is clearly not offering clinical outcomes needed for RCC. Integrative medicine research that includes a whole systems approach with a focus on quality of life and extended survival in renal cell carcinoma should include the mentioned medicinal mushrooms to create new strategies in treatment.
https://www.mdpi.com/2227-9059/8/5/135	3.5	PSK as an adjuvant to vaccines has been demonstrated to induce the production of cytokines (e.g., IL-12, TNF-α, and IL6) in these cells both in vitro and in vivo [84]. Hence, the immunostimulatory effect coupled with direct toxicity to cancer cells by C. versicolor polysaccharides implies application even more than an adjuvant therapy. The evidence for signal transduction pathways, including that for TLR4 as well as other cell surface recognition markers of the polysaccharides (e.g., Dectin-1 as a β-glucan receptor), are evolving current research	For example, PSK as an adjuvant to vaccines has been demonstrated to induce the production of cytokines (e.g., IL-12, TNF-α, and IL6) in these cells both in vitro and in vivo [84]. Hence, the immunostimulatory effect coupled with direct toxicity to cancer cells by C. versicolor polysaccharides implies application even more than an adjuvant therapy. The evidence for signal transduction pathways, including that for TLR4 as well as other cell surface recognition markers of the polysaccharides (e.g., Dectin-1 as a β-glucan receptor), are evolving current research. The structural moieties of the polysaccharides that attribute to the various pharmacological effects also need further research.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3017241/	1	We demonstrate that PSK is a selective TLR2 agonist, and the activation of dendritic cells (DC) and T cells by PSK is dependent on TLR2. Oral administration of PSK in neu transgenic mice significantly inhibits breast cancer growth. Selective depletion of specific cell populations suggests that the anti-tumor effect of PSK is dependent on both CD8+ T cell and NK cells, but not CD4+ T cells. PSK does not inhibit tumor growth in TLR2−/− mice suggesting the anti-tumor effect is mediated by TLR2	In summary, results from the current study demonstrate that PSK is a selective TLR2 agonist. The effect of PSK on DC and T cells is dependent on TLR2 activation. Oral PSK inhibits breast cancer growth in neu transgenic mice and the anti-tumor effect is dependent on both CD8+ T cells and NK cells. Results from this study elucidate the mechanism of action of this mushroom based natural product and may lead to more effective methods of therapeutically exploiting the anti-tumor effects of PSK
https://europepmc.org/article/PMC/3206987#	1	Clinical trials in Japan have shown that oral intake of PSK significantly extended survival at five years or beyond in patients with different types of cancer, especially stomach and colorectal cancer (27-29). Using HEK293 cells transfected with different TLRs, we demonstrated that PSK is a selective and potent TLR2 agonist (25). We further showed that the anti-tumor effect of PSK in a mouse model of breast cancer is dependent on both CD8 T cells and NK cells	In summary, our study indicates the potential of using PSK, a natural product with potent TLR2 agonist activity, to augment the function of NK cells and enhance ADCC. The major advantage of PSK as compared to other TLR agonists that are currently evaluated in clinical trials, such as CpG, imiquimod, or poly I:C, is its known safety profile. PSK is a mushroom extract that has been widely used in Asian countries for its immune potentiating and anti-tumor effects.
https://pmc.ncbi.nlm.nih.gov/articles/PMC3095629/	1	Here, we report that PSP, an active component extracted from the mushroom Turkey tail (also known as Coriolus versicolor), is effective in targeting prostate CSCs. We found that treatment of the prostate cancer cell line PC-3 with PSP led to the down-regulation of CSC markers (CD133 and CD44) in a time and dose-dependent manner. Meanwhile, PSP treatment not only suppressed the ability of PC-3 cells to form prostaspheres under non-adherent culture conditions, but also inhibited their tumorigenicity in vivo, further proving that PSP can suppress prostate CSC properties	Whereas four weeks of PSP oral consumption at 200 mg/kg failed to produce any differences in PIN development, complete inhibition of prostate tumor formation was achieved after 20 weeks of oral PSP feeding at 300 mg/Kg. Meanwhile, the suppression of PIN formation by PSP further suggested that the chemopreventive effect of PSP may due to suppression of the tumor initiation at early stage. The extremely low toxicity and the highly potent anti-CSC effect of PSP warrants further evaluation of its chemopreventive effect in human clinical trials.