CD39 Identifies the CD4 + Tumor-Specific T-cell Population in Human Cancer.
| Autor: | Kortekaas KE; Department of Gynecology, Leiden University Medical Center, Leiden, the Netherlands., Santegoets SJ; Department of Medical Oncology, Oncode Institute, Leiden University Medical Center, Leiden, the Netherlands., Sturm G; Institute of Bioinformatics, Biocenter, Medical University of Innsbruck, Innsbruck, Austria., Ehsan I; Department of Medical Oncology, Oncode Institute, Leiden University Medical Center, Leiden, the Netherlands., van Egmond SL; Department of Otolaryngology and Head and Neck Surgery, Leiden University Medical Center, Leiden, the Netherlands., Finotello F; Institute of Bioinformatics, Biocenter, Medical University of Innsbruck, Innsbruck, Austria., Trajanoski Z; Institute of Bioinformatics, Biocenter, Medical University of Innsbruck, Innsbruck, Austria., Welters MJP; Department of Medical Oncology, Oncode Institute, Leiden University Medical Center, Leiden, the Netherlands., van Poelgeest MIE; Department of Gynecology, Leiden University Medical Center, Leiden, the Netherlands., van der Burg SH; Department of Medical Oncology, Oncode Institute, Leiden University Medical Center, Leiden, the Netherlands. shvdburg@lumc.nl. |
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| Jazyk: | angličtina |
| Zdroj: | Cancer immunology research [Cancer Immunol Res] 2020 Oct; Vol. 8 (10), pp. 1311-1321. Date of Electronic Publication: 2020 Aug 05. |
| DOI: | 10.1158/2326-6066.CIR-20-0270 |
| Abstrakt: | 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 show that tumor-specific CD4 + T cells were predominantly present in the CD39 + subset of tumor-infiltrating lymphocytes (TIL). The CD39 + CD4 + and CD8 + TILs were detected in three different tumor types, and displayed an activated (PD-1 + , HLA-DR + ) effector memory phenotype. CD4 + CD39 + single-cell RNA-sequenced TILs shared similar well-known activation, tissue residency, and effector cell-associated genes with CD8 + CD39 + CD103 + TILs. Finally, analysis of directly ex vivo cell-sorted and in vitro expanded pure populations of CD39-positive and negative CD4 + and CD8 + TILs revealed that tumor-specific antigen reactivity was almost exclusively detected among CD39 + cells. Immunotherapy of cancer is based on the activation of tumor-reactive CD4 + and CD8 + T cells. We show that the expression of CD39 can be used to identify, isolate, and expand tumor-reactive T-cell populations in cancers. (©2020 American Association for Cancer Research.) |
| Databáze: | MEDLINE |
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