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CD39+ regulatory T cells accumulate in colon adenocarcinomas and display markers of increased suppressive function

Journal article
Authors Filip Ahlmanner
Patrik Sundström
Paulina Akeus
Jenny Eklöf
Lars Börjesson
Bengt Gustavsson
Elinor Bexe-Lindskog
Sukanya Raghavan
Marianne Quiding-Järbrink
Published in Oncotarget
Volume 9
Issue 97
Pages 36993-37007
ISSN 1949-2553
Publication year 2018
Published at Institute of Clinical Sciences, Department of Surgery
Institute of Biomedicine, Department of Microbiology and Immunology
Pages 36993-37007
Language en
Links doi.org/10.18632/oncotarget.26435
Keywords Adenosine, CD39, Colon cancer, Immune checkpoint molecules, Regulatory T cells
Subject categories Cancer and Oncology, Immunology in the medical area

Abstract

Increasing knowledge of the function and regulation of tumor-infiltrating lymphocytes has led to new insights in cancer immunotherapy. Regulatory T cells (Treg) accumulate in colon tumors, and we recently showed that CD39+ Treg from cancer patients inhibit transendothelial migration of conventional T cells. CD39 mediates the hydrolysis of ATP to immunosuppressive adenosine and adds to the immunosuppressive effects of Treg. Here, we further investigated the regulatory features of intratumoral CD39+ Treg in colon cancer. Using flow cytometry analyses of cells from 46 colon cancer patients, we confirm the accumulation of CD39+ Treg in the tumor tissue compared to unaffected colon tissue, and also show that tumor-infiltrating Treg express more CD39 and Foxp3 on a per cell basis. Furthermore, CD39+ Treg in tumors express markers indicating increased turnover and suppressive ability. In particular, tumor-infiltrating CD39+ Treg have high expression of surface molecules related to immunosuppression, such as ICOS, PD-L1 and CTLA-4. Functional suppression assays also indicate potent suppressive capacity of CD39+ Treg on proliferation and IFN-γ secretion by conventional T cells. In conclusion, our results identify tumor-infiltrating CD39+ Treg as a numerous and potentially important immunosuppressive subset, and suggest that immunotherapy aimed at reducing the activity of CD39+ Treg may be particularly useful in the setting of colon cancer. © 2018 Ahlmanner et al.

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