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“High Treg” Inflammations Promote (Most) Non-Hematologic Cancers While “Low Treg” Inflammations Promote Lymphoid Cancers

Authors Elkoshi Z

Received 11 February 2020

Accepted for publication 29 April 2020

Published 21 May 2020 Volume 2020:13 Pages 209—221

DOI https://doi.org/10.2147/JIR.S249384

Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 3

Editor who approved publication: Dr Ning Quan


Zeev Elkoshi

Research and Development Department, Taro Pharmaceutical Industries Ltd, Haifa, Israel

Correspondence: Zeev Elkoshi Email zeev.elkoshi@gmail.com

Abstract: In an earlier publication, a binary classification of chronic diseases has been proposed. Chronic diseases were classified as “high Treg” or “low Treg” diseases depending on whether the pro-inflammatory or the anti-inflammatory arms of the immune response are deficient. The present work uses this model to analyze the interplay between cancer and the immune system, based on published literature. The work leans upon the etiology of alcohol and tobacco-related malignancies. The main conclusions are: triggers of specific “high Treg” immune reaction promote most non-hematologic cancers, whereas triggers of “low Treg” immune reaction promote lymphomas. The opposite is also true: triggers of specific “high Treg” immune reaction suppress lymphoma, whereas triggers of “low Treg” immune reaction suppress non-hematologic cancers. Both lymphoma and autoimmune diseases are “low Treg” conditions. For this reason, both are promoted by the same panel of “low Treg” bacteria and parasites and are inhibited by “high Treg” triggers. For example, alcohol consumption, a “high Treg” trigger, protects against lymphoma and autoimmune hypothyroidism. In addition, the same immune-modulatory drugs are effective in the treatment of both lymphoma and autoimmune diseases. Like other cancers, lymphoma transforms from a “low Treg” type at early stage of the disease into a “high Treg” type at advanced stages. However, lymphoma is distinguished from most other cancers by the length of time it dwells at an indolent “low Treg” state (many years) before lymphoma cells sensitivity to transforming growth factor-beta is impaired. This impairment stimulates the switch from “low Treg” into “high Treg” response and results in immune escape. The application of this analysis to the pharmacological activity of checkpoint inhibitors forecasts that checkpoint inhibitors would not be effective in low-grade, indolent lymphomas. As of now, checkpoint inhibitors are approved for the treatment of advanced lymphoma only.

Keywords: regulatory T cells, lymphoma, cancer, alcohol consumption, cigarette smoking, checkpoint inhibitors, high Treg, low Treg, inflammation, autoimmune diseases, immune escape

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