Regulatory T‐cell development in the tumor microenvironment

Abstract

Regulatory T (Treg) cells are required for maintaining self‐tolerance and preventing the development of autoimmune diseases. However, Treg cells are abundant in tumors and suppress antitumor immunity, contributing to tumor development and growth. Thus, the selective deletion of tumor‐infiltrating Treg cells is important for successful Treg cell‐targeted therapies, providing effective antitumor immunity without inducing deleterious autoimmune disorders. Advancements in sequencing technologies have exposed the diversity and heterogeneity of human Treg cells during activation and differentiation, further emphasizing the importance of understanding tumor‐infiltrating Treg cells for the development of Treg cell‐targeted therapies. This review provides an overview of the classification and function of Treg cells and summarizes recent knowledge on the activation and differentiation of Treg cells in the tumor microenvironment.

Gastric Cancer and the Immune System: The Key to Improving Outcomes?

“…Lymphocytes include all T and B cells originally derived from bone marrow progenitors. Circulating immature precursors of T cells enter the thymus and mature into CD4+CD8+ T cells, which subsequently become selected as single positive CD4+ or CD8+ T cells if they bind self-peptide/MHC complexes with low affinity [ 16 ]. Cells that recognize MHC I will become CD8+ T cells with cytotoxic effects on tumor cells and virus-infected cells, while cells that recognize MHC II become CD4+ T cells [ 17 ].…”

“…These include Th1 (which secrete IFN-γ and TNF-α and activate macrophages), Th2 (which secrete IL-4 and IL-5 and stimulate neutrophil attraction), and Th17 cells (which secrete IL-17) [ 17 , 18 ]. Certain T cells will have a high affinity of self-peptide/MHC complexes, and they may be induced into a regulatory T cell (Treg) phenotype through cytokines [ 16 ]. Treg have the ability to cause immune suppression via multiple mechanisms: expression of CTLA-4 to inhibit antigen presenting cells, consumption of IL-2 (which is a pro-inflammatory cytokine), secretion of immune cell inhibitory cytokines (IL-10, IL-35, and TGF-β), and induced immune cell death via granzyme and perforin [ 16 ].…”

“…Certain T cells will have a high affinity of self-peptide/MHC complexes, and they may be induced into a regulatory T cell (Treg) phenotype through cytokines [ 16 ]. Treg have the ability to cause immune suppression via multiple mechanisms: expression of CTLA-4 to inhibit antigen presenting cells, consumption of IL-2 (which is a pro-inflammatory cytokine), secretion of immune cell inhibitory cytokines (IL-10, IL-35, and TGF-β), and induced immune cell death via granzyme and perforin [ 16 ]. Tumor cells themselves can also secrete anti-inflammatory cytokines, such as IL-10 and TGF-β, as well as promote the generation of Treg and produce FAS-ligand to induce apoptosis of activated T cells [ 19 ].…”

The Microbiome-Immune Axis Therapeutic Effects in Cancer Treatments

“…Another possible mechanism influencing cancer immune avoidance is likely related to regulatory T (Treg) cell function or their anti-inflammatory cytokine secretions. These cells are responsible for modifying the production of immune suppressive mediators, tolerance and immune deviation [ 6 - 9 ]. Therefore, it is necessary the development of strategies that enhance immune responses under cancer environments to promote the efficacy of current cancer therapies.…”

“…Another possible mechanism influencing cancer immune avoidance is likely related to regulatory T (Treg) cell function or their anti-inflammatory cytokine secretions. These cells are responsible for modifying the production of immune suppressive mediators, tolerance and immune deviation [6][7][8][9]. Therefore, it is necessary the development of strategies that enhance immune responses under cancer environments to promote the efficacy of current cancer therapies.Recently, microbiota indicating varied microorganisms such as bacteria, virus, fungi and archaea in most living organisms has been shown to exert great potential in affecting human health and disease, particularly controlling the immune system [10][11][12].…”