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Cancer Health Main Forums => Cancer Research News & Studies => Topic started by: danialthomas on March 13, 2021, 05:07:06 pm

Title: Why do so few people benefit from “breakthrough” cancer immunotherapy?
Post by: danialthomas on March 13, 2021, 05:07:06 pm
When the first immunotherapy drug ipilimumab (Yervoy) was FDA approved in 2011, immunotherapy was hailed as breakthrough in cancer treatment. This new therapy harnessed the power of the body’s own immune system to fight cancer. Fast forward to today and, unfortunately, only a minority of cancer patients actually benefit from immunotherapy in terms of tumor shrinkage, and even fewer experience long-term survival.
Why did immunotherapy not live up to the hype? It turns out that simply “revving up” the immune system is not enough. Having plenty of natural-killer (NK) cells, cytotoxic T-cells (CTCs), and M1 macrophages is insufficient. Tumors still have ways to avoid immune destruction which include:

• Recruitment of immunosuppressive T-regulatory cells (Tregs) and myeloid cells.
• Recruitment of tumor-killing M1 macrophages and polarizing them into tumor-promoting M2 macrophages (also known as tumor-associated macrophages or TAMs).
• Malignant cell exposure to blood platelets.
• Iron-induced parafibrin formation blocking immune-mediated destruction.
• Tumor collagen density preventing adequate infiltration of immune cells.
• Lack of sufficient energy by immune cells.
To improve the efficacy of immunotherapy, it is important to:
• Reduce Tregs and myeloid cells using ivermectin.
• Repolarize tumor-promoting M2 macrophages into tumor-killing M1 macrophages using onionin A, a sulfur-containing compound from onions.
• Reduce platelet aggregation and reduce tumor density using pentoxifylline (Trental).
• Block formation of parafibrin using curcumin, EGCG, ferulic acid, magnesium, and sodium selenite.
• Supplement with creatine. Creatine, a supplement that is popular with athletes and bodybuilders, serves as a “molecular battery” for immune cells by storing and distributing energy to power their fight against cancer.

Please note that this information for educational purposes only. It is not intended or implied to be a substitute for professional medical advice, diagnosis, treatment, and monitoring by your personal physician. Therefore, I cannot give dosages for the above-mentioned supplements and medications. That is for your personal physician to determine.


Dr. Daniel Thomas, DO, MS
Mount Dora, Florida


References:
Bałan BJ, Demkow U, Skopiński P, et al. The effect of pentoxifylline on L-1 sarcoma tumor growth and angiogenesis in Balb/c mice. Cent Eur J Immunol. 2017;42(2):131-139.
Draganov D, Han Z, Rana A, Bennett N, Irvine DJ, Lee PP. Ivermectin converts cold tumors hot and synergizes with immune checkpoint blockade for treatment of breast cancer. NPJ Breast Cancer. 2021 Mar 2;7(1):22.
Kim JH, Shin BC, Park WS, Lee J, Kuh HJ. Antifibrotic effects of pentoxifylline improve the efficacy of gemcitabine in human pancreatic tumor xenografts. Cancer Sci. 2017 Dec;108(12):2470-2477.
Lipinski B. Iron-induced parafibrin formation in tumors fosters immune evasion.
Stefano Di Biase, Xiaoya Ma, Xi Wang, Jiaji Yu, Yu-Chen Wang, Drake J. Smith, Yang Zhou, Zhe Li, Yu Jeong Kim, Nicole Clarke, Angela To, Lili Yang; Creatine uptake regulates CD8 T cell antitumor immunity. J Exp Med 2 December 2019; 216 (12): 2869–2882.
Tsuboki, J., Fujiwara, Y., Horlad, H. et al. Onionin A inhibits ovarian cancer pro-gression by suppressing cancer cell proliferation and the protumour function of macrophages. Sci Rep 6, 29588 (2016).