CD39 Identifies the CD4+ Tumor-Specific T-cell Population in Human Cancer
- 1 October 2020
- journal article
- research article
- Published by American Association for Cancer Research (AACR) in Cancer Immunology Research
- Vol. 8 (10), 1311-1321
- https://doi.org/10.1158/2326-6066.cir-20-0270
Abstract
The accumulation of tumor-specific CD4+ and CD8+ effector T cells is key to an effective antitumor response. Locally, CD4+ T cells promote the recruitment and effector function of tumor-specific CD8+ T cells and activate innate killer cells in the tumor. Here, we showed that tumor-specific CD4+ T cells were predominantly present in the CD39+ subset of tumor-infiltrating lymphocytes (TIL). The CD39+ CD4+ and CD8+ TIL were detected in 3 different tumor types, and displayed an activated (PD-1+, HLA-DR+) effector memory phenotype. CD4+CD39+ single cell RNA sequenced TIL shared similar well-known activation, tissue residency, and effector cell-associated genes with CD8+CD39+CD103+ TIL. Finally, analysis of directly ex-vivo cell sorted and in vitro expanded pure populations of CD39-positive and negative CD4+ and CD8+ TIL revealed that tumor-specific antigen reactivity was almost exclusively detected among CD39+ cells.Keywords
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Funding Information
- Dutch Cancer Society
- Oncode Institute
- Austrian Science Fund (T 974-B30)
- European Research Council (786295)
- Austrian Science Fund (I 3978)
- German Research Foundation (TRR 241)
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