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Regulatory T cells specifically suppress conventional CD8 alpha beta T cells in intestinal tumors of APC(Min/+) mice

Journal article
Authors Louis Szeponik
Paulina Akeus
William Rodin
Sukanya Raghavan
Marianne Quiding-Järbrink
Published in Cancer Immunology, Immunotherapy
Volume 69
Pages 1279-1292
ISSN 0340-7004
Publication year 2020
Published at Institute of Biomedicine, Department of Microbiology and Immunology
Pages 1279-1292
Language en
Links dx.doi.org/10.1007/s00262-020-02540...
Keywords Regulatory T cells, APCmin, +, Colon cancer, Tumor-infiltrating, lymphocytes, Anti-tumor immunity, chemokine production, colon-cancer, accumulation, promote, gamma, angiogenesis, mechanisms, landscape, depletion, responses, Oncology, Immunology
Subject categories Microbiology in the medical area

Abstract

The presence of activated T cells in colorectal cancer tissues is a strong predictor of patient survival. Our previous studies have shown that regulatory T cells (Treg) are able to reduce T cell transendothelial migration in vitro and accumulation of effector T cells in intestinal tumors in vivo in the murine APC(Min/+) model for microsatellite stable intestinal tumors. In this study, we investigated the effect of Treg depletion on the density and effector functions of different TCR alpha beta(+) and TCR gamma delta(+) T cell populations in intestinal tumors. We used the APC(Min/+)\DEREG mouse model, which harbor a diphtheria toxin receptor under the control of the FOXP3 promoter, to deplete Treg in tumor bearing mice. We found that the density of conventional TCR alpha beta(+)CD8 alpha beta(+) T cells was significantly increased in Treg-depleted tumors in comparison with Treg-proficient tumors. Furthermore, TCR alpha beta(+)CD8 alpha beta(+) T cells showed increased proliferation and activation as well as increased Granzyme B and IFN-gamma production in Treg-depleted tumors. In sharp contrast, the densities and effector functions of TCR alpha beta(+)CD8 alpha alpha(+) T cells and TCR gamma delta(+) T cells remained unchanged by Treg depletion. We also documented a distinct population of IL-17A(+)TNF(+) TCR gamma delta(+)CD8(-) T cells in tumors, which were not affected by Treg depletion. We conclude that Treg depletion affects only conventional TCR alpha beta(+)CD8 alpha beta(+) T cells in intestinal tumors, while unconventional T cells and T cells in unaffected tissue are not altered. Immunotherapies aimed at depleting Treg from tumors may thus be a viable option for reinvigoration of conventional cytotoxic T cells with a Th1 cytokine profile.

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