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Open Access 01-07-2020 | Colorectal Cancer | Original Article

Regulatory T cells specifically suppress conventional CD8αβ T cells in intestinal tumors of APC^Min/+ mice

Authors: Louis Szeponik, Paulina Akeus, William Rodin, Sukanya Raghavan, Marianne Quiding-Järbrink

Published in: Cancer Immunology, Immunotherapy | Issue 7/2020

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 TCRαβ⁺ and TCRγδ⁺ 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 TCRαβ⁺CD8αβ⁺ T cells was significantly increased in Treg-depleted tumors in comparison with Treg-proficient tumors. Furthermore, TCRαβ⁺CD8αβ⁺ T cells showed increased proliferation and activation as well as increased Granzyme B and IFN-γ production in Treg-depleted tumors. In sharp contrast, the densities and effector functions of TCRαβ⁺CD8αα⁺ T cells and TCRγδ⁺ T cells remained unchanged by Treg depletion. We also documented a distinct population of IL-17A⁺TNF⁺ TCRγδ⁺CD8⁻ T cells in tumors, which were not affected by Treg depletion. We conclude that Treg depletion affects only conventional TCRαβ⁺CD8αβ⁺ 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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Title: Regulatory T cells specifically suppress conventional CD8αβ T cells in intestinal tumors of APCMin/+ mice
Authors: Louis Szeponik
Paulina Akeus
William Rodin
Sukanya Raghavan
Marianne Quiding-Järbrink
Publication date: 01-07-2020
Publisher: Springer Berlin Heidelberg
Keywords: Colorectal Cancer
Colorectal Cancer
Published in: Cancer Immunology, Immunotherapy / Issue 7/2020
Print ISSN: 0340-7004
Electronic ISSN: 1432-0851
DOI: https://doi.org/10.1007/s00262-020-02540-9

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