CD39+ conventional CD4+ T cells with exhaustion traits and cytotoxic potential infiltrate tumors and expand upon CTLA-4 blockade
| Title: | CD39+ conventional CD4+ T cells with exhaustion traits and cytotoxic potential infiltrate tumors and expand upon CTLA-4 blockade |
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| Authors: | Sabrina N. Bossio, Carolina Abrate, Jimena Tosello Boari, Constanza Rodriguez, Fernando P. Canale, María C. Ramello, Valentina Brunotto, Wilfrid Richer, Dario Rocha, Christine Sedlik, Anne Vincent-Salomon, Edith Borcoman, Andres Del Castillo, Adriana Gruppi, Elmer Fernandez, Eva V. Acosta Rodríguez, Eliane Piaggio, Carolina L. Montes |
| Source: | OncoImmunology, Vol 12, Iss 1 (2023) |
| Publisher Information: | Taylor & Francis Group, 2023. |
| Publication Year: | 2023 |
| Collection: | LCC:Immunologic diseases. Allergy LCC:Neoplasms. Tumors. Oncology. Including cancer and carcinogens |
| Subject Terms: | Cancer, CD39, conventional CD4+ T cells, cytotoxicity, exhaustion, Immunologic diseases. Allergy, RC581-607, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282 |
| More Details: | Conventional CD4+ T (Tconv) lymphocytes play important roles in tumor immunity; however, their contribution to tumor elimination remains poorly understood. Here, we describe a subset of tumor-infiltrating Tconv cells characterized by the expression of CD39. In several mouse cancer models, we observed that CD39+ Tconv cells accumulated in tumors but were absent in lymphoid organs. Compared to tumor CD39− counterparts, CD39+ Tconv cells exhibited a cytotoxic and exhausted signature at the transcriptomic level, confirmed by high protein expression of inhibitory receptors and transcription factors related to the exhaustion. Additionally, CD39+ Tconv cells showed increased production of IFN[Formula: see text], granzyme B, perforin and CD107a expression, but reduced production of TNF. Around 55% of OVA-specific Tconv from B16-OVA tumor-bearing mice, expressed CD39. In vivo CTLA-4 blockade induced the expansion of tumor CD39+ Tconv cells, which maintained their cytotoxic and exhausted features. In breast cancer patients, CD39+ Tconv cells were found in tumors and in metastatic lymph nodes but were less frequent in adjacent non-tumoral mammary tissue and not detected in non-metastatic lymph nodes and blood. Human tumor CD39+ Tconv cells constituted a heterogeneous cell population with features of exhaustion, high expression of inhibitory receptors and CD107a. We found that high CD4 and ENTPD1 (CD39) gene expression in human tumor tissues correlated with a higher overall survival rate in breast cancer patients. Our results identify CD39 as a biomarker of Tconv cells, with characteristics of both exhaustion and cytotoxic potential, and indicate CD39+ Tconv cells as players within the immune response against tumors. |
| Document Type: | article |
| File Description: | electronic resource |
| Language: | English |
| ISSN: | 2162402X 2162-402X |
| Relation: | https://doaj.org/toc/2162-402X |
| DOI: | 10.1080/2162402X.2023.2246319 |
| Access URL: | https://doaj.org/article/c2c7022bc10c4d4d97766bb302e5a761 |
| Accession Number: | edsdoj.2c7022bc10c4d4d97766bb302e5a761 |
| Database: | Directory of Open Access Journals |
| ISSN: | 2162402X |
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| DOI: | 10.1080/2162402X.2023.2246319 |
| Published in: | OncoImmunology |
| Language: | English |