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

• Published in: Oncotarget 2018-12, Vol.9 (97), p.36993-37007
• Main Authors: Ahlmanner, Filip, Sundström, Patrik, Akeus, Paulina, Eklöf, Jenny, Börjesson, Lars, Gustavsson, Bengt, Lindskog, Elinor Bexe, Raghavan, Sukanya, Quiding-Järbrink, Marianne
• Format: Article
• Language: English
• Subjects: Adenosine; Cancer and Oncology; Cancer och onkologi; CD39; Colon cancer; Immune checkpoint molecules; Immunologi inom det medicinska området; Immunology in the Medical Area; Regulatory T cells; Research Paper
• ISSN: 1949-2553; 1949-2553
• DOI: 10.18632/oncotarget.26435

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.