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Dynamic biomarkers indicate the immunological benefits provided by Ganoderma spore powder in post-operative breast and lung cancer patients

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Abstract

Background

T lymphocyte are a strong indicator of treatment immune response. This study was aimed to determine the utility of T lymphocyte subsets, cytokines and inflammatory biomarkers in predicting the immunological benefits of Ganoderma spore powder (G. lucidum) in post-operative patients with breast and lung cancer.

Methods

We prospectively evaluated 120 breast and lung cancer patients with or without G. lucidum. T lymphocyte subsets with relative cytokines were detected using flow cytometry and PCR and assessed by Spearman correlation analysis. The relationships between albumin-to-globulin ratio (AGR) and neutrophil–to-lymphocyte ratio (NLR) with G. lucidum treatment and prognosis were analyzed using Kaplan–Meier and Cox regression methods.

Results

The prevalence of CD3 + CD4 + , CD3 + HLADR- types was higher in G. lucidum group compared to control, whilst CD4 + CD25 + Treg, CD3 + HLADR + cell types was lower. IL-12 levels were significantly higher during the treatment period which negatively impacted levels of IL-10. Other immunosuppressive factors such as COX2 and TGF-β1 had lower prevalence in treated patients. Correlation analysis showed a positive relationship between IL-10 and CD28. IL-2 was positively related to TGF-β1, whilst it was negatively related to CD3. Kaplan–Meier analysis suggested that low AGR/high NLR was related to poor progression free survival (PFS) and overall survival (OS). A combination of high AGR and low NLR may predicted treatment benefits associated with PFS and OS.

Conclusions

Our findings show that T lymphocyte subsets combined with relevant cytokines and AGR/NLR inflammatory predictors may help to identify patients most likely to benefit from the immunological enhancements from G. lucidum treatment.

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Data availability

Data are available upon reasonable request. No additional data are available for this study in repositories. Inquiries concerning the data may be made to the corresponding author.

References

  1. Lancet T. Lung cancer: some progress, but still a lot more to do. Lancet. 2019;394(10212):1880. https://doi.org/10.1016/S0140-6736(19)32795-3.

    Article  Google Scholar 

  2. Nuzzolese I, Montemurro F. Attrition in metastatic breast cancer: a metric to be reported in randomised clinical trials? Lancet Oncol. 2020;21(1):21–4. https://doi.org/10.1016/S1470-2045(19)30792-2.

    Article  PubMed  Google Scholar 

  3. Matikas A, Margolin S, Hellström M, et al. Long-term safety and survival outcomes from the Scandinavian Breast Group 2004–1 randomized phase II trial of tailored dose-dense adjuvant chemotherapy for early breast cancer. Breast Cancer Res Treat. 2018;168(2):349–55.

    Article  CAS  Google Scholar 

  4. Xu J, Li P. Researches and application of Ganoderma spores powder. Adv Exp Med Biol. 2019;1181:157–86.

    Article  CAS  Google Scholar 

  5. Zhang Y, Jiang Y, Zhang M, Zhang L. Ganoderma sinense polysaccharide: an adjunctive drug used for cancer treatment. Prog Mol Biol Transl Sci. 2019;163:165–77.

    Article  CAS  Google Scholar 

  6. Zhu LF, Yao ZC, Ahmad Z, Li JS, Chang MW. Synthesis and evaluation of herbal chitosan from Ganoderma lucidum spore powder for biomedical applications. Sci Rep. 2018;8:14608.

    Article  Google Scholar 

  7. Dudhgaonkar S, Thyagarajan A, Sliva D. Suppression of the inflammatory response by triterpenes isolated from the mushroom Ganoderma lucidum. Int Immunopharmacol. 2009;9(11):1272–80.

    Article  CAS  Google Scholar 

  8. Cheng S, Sliva D. Ganoderma lucidum for cancer treatment: we are close but still not there. Integr Cancer Ther. 2015;14(3):249–57.

    Article  CAS  Google Scholar 

  9. Ma QY, Chen J, Zhao J. Follicular cytotoxic CD8 T cells present high cytokine expression, and are more susceptible to Breg-mediated suppression in non-small cell lung cancer. Immunol Res. 2020;68(1):54–62.

    Article  CAS  Google Scholar 

  10. Xuan Q, Yang Y, Ji H, et al. Combination of the preoperative albumin to globulin ratio and neutrophil to lymphocyte ratio as a novel prognostic factor in patients with triple negative breast cancer. Cancer Manag Res. 2019;31(11):5125–31.

    Article  Google Scholar 

  11. Li Y, Qiao S, Li G. Effect of ganoderma lucidum powder on anti-tumor and improving immunity. Chin J Chron Dis Prevent Control. 2004;12(4):156–60.

    Google Scholar 

  12. Wang Y, Yang J-M, Wang Y. Immunomodulatory effects of ganoderma lucidum spores. Chinese Edible Fungi. 2002;21(1):156–60.

    Google Scholar 

  13. Liang Y, He M, Fan X, et al. An abnormal elevation of serum CA72–4 by ganoderma lucidum spore powder. Ann Clin Lab Sci. 2013;43(3):337–40.

    CAS  PubMed  Google Scholar 

  14. Boh B. Ganoderma lucidum: a potential for biotechnological production of anti-cancer and immunomodulatory drugs. Recent Pat Anticancer Drug Discov. 2013;8(3):255–87.

    Article  CAS  Google Scholar 

  15. Egen JG, Ouyang W, Wu LC. Human anti-tumor immunity: insights from immunotherapy clinical trials. Immunity. 2020;52(1):36–54.

    Article  CAS  Google Scholar 

  16. Zhao H, Zhang Q, Zhao L, et al. Spore powder of Ganoderma lucidum improves cancer-related fatigue in breast cancer patients undergoing endocrine therapy: a pilot clinical trial. Evid Based Complement Alternat Med. 2012;2012:809614.

    PubMed  Google Scholar 

  17. Speiser DE, Ho PC, Verdeil G. Regulatory circuits of T cell function in cancer. Nat Rev Immunol. 2016;16(10):599–611.

    Article  CAS  Google Scholar 

  18. Karagoz B, Bilgi O, Gumus M, et al. CD8+CD28- cells and CD4+CD25+ regulatory T cells in the peripheral blood ofadvanced stage lung cancer patients. Med Oncol. 2010;27(1):29–33.

    Article  Google Scholar 

  19. Su J, Su L, Li D, et al. Antitumor activity of extract from the Sporoderm-breaking spore of Ganoderma lucidum: restoration on exhausted cytotoxic T cell with gut microbiota remodeling. Front Immunol. 2018;9:1765.

    Article  Google Scholar 

  20. Li CW, Osman R, Menconi F, et al. Flexible peptide recognition by HLA-DR triggers specific autoimmune T-cell responses in autoimmune thyroiditis and diabetes. J Autoimmun. 2017;76:1–9.

    Article  Google Scholar 

  21. Saraiva DP, Jacinto A, Borralho P, et al. HLA-DR in cytotoxic T lymphocytes predicts breast cancer patients’ response to neoadjuvant chemotherapy. Front Immunol. 2018;13(9):2605.

    Article  Google Scholar 

  22. Wang X, Lin Z. Immunomodulating effect of Ganoderma (Lingzhi) and possible mechanism. Adv Exp Med Biol. 2019;1182:1–37.

    Article  CAS  Google Scholar 

  23. Zeng P, Chen Y, Zhang L, Xing M, et al. Ganoderma lucidum polysaccharide used for treating physical frailty in China. Prog Mol Biol Transl Sci. 2019;163:179–219.

    Article  CAS  Google Scholar 

  24. Sun LX, Li WD, Lin ZB, Duan XS, Xing EH, Jiang MM, et al. Cytokine production suppression by culture supernatant of B16F10 cells and amelioration by Ganoderma lucidum polysaccharides in activated lymphocytes. Cell Tissue Res. 2015;360(2):379–89. https://doi.org/10.1007/s00441-014-2083-6.

    Article  CAS  PubMed  Google Scholar 

  25. Zhu L, Tu H, Liang Y, et al. MiR-218 produces anti-tumor effects on cervical cancer cells in vitro. World J Surg Oncol. 2018;16(1):204.

    Article  Google Scholar 

  26. Che D, Zhang S, Jing Z, et al. Macrophages induce EMT to promote invasion of lung cancer cells through the IL-6-mediated COX-2/PGE(2)/β-catenin signalling pathway. Mol Immunol. 2017;90:197–210.

    Article  CAS  Google Scholar 

  27. Mateu-Jimenez M, Curull V, Pijuan L, Sánchez-Font A, et al. Systemic and tumor Th1 and Th2 inflammatory profile and macrophages in lung cancer: influence of underlying chronic respiratory disease. J Thorac Oncol. 2017;12(2):235–48.

    Article  Google Scholar 

  28. Habijanic J, Berovic M, Boh B, et al. Submerged cultivation of Ganoderma lucidum and the effects of its polysaccharides on the production of human cytokines TNF-α, IL-12, IFN-γ, IL-2, IL-4, IL-10 and IL-17. N Biotechnol. 2015;32(1):85–95.

    Article  CAS  Google Scholar 

  29. Cizmarikova M. The efficacy and toxicity of using the Lingzhi or Reishi medicinal mushroom, Ganoderma lucidum (Agaricomycetes), and its products in chemotherapy (Review). Int J Med Mushrooms. 2017;19(10):861–77.

    Article  Google Scholar 

  30. Galon J, Bruni D. Tumor immunology and tumor evolution: intertwined histories. Immunity. 2020;52(1):55–81.

    Article  CAS  Google Scholar 

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Acknowledgements

The G. lucidum was supplied by Jiangxi Tianhai Group (Batch number 2014AA022206-LC02). The clinical data detection was supported by Harbin Medical University Cancer Hospital.

Funding

National High Technology Research and Development Program (863 Program), Subject No.: 2014AA022206, China.

Author information

Authors and Affiliations

Authors

Contributions

QZ designed and directed this study. YD drafted the initial manuscript and participated in trial monitoring. JM and DT modified the manuscript and conducted statistical analysis. All authors devoted to the revision of the manuscript and approved the final version.

Corresponding authors

Correspondence to D. Tang or Q. Zhang.

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Conflict of interest

The authors report no conflicts of interest in this work.

Ethics approval

This study, including the procedures for patient enrollment and recruitment, was approved by the Institutional Review Board (IRB) of the Harbin Medical University Cancer Hospital.

Consent to participate

All patients who participated in the study provided written informed consent. This study was conducted in accordance with the Declaration of Helsinki.

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Obtained.

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Cite this article

Deng, Y., Ma, J., Tang, D. et al. Dynamic biomarkers indicate the immunological benefits provided by Ganoderma spore powder in post-operative breast and lung cancer patients. Clin Transl Oncol 23, 1481–1490 (2021). https://doi.org/10.1007/s12094-020-02547-9

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  • DOI: https://doi.org/10.1007/s12094-020-02547-9

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