CD39+ conventional CD4+ T cells with exhaustion traits and cytotoxic potential infiltrate tumors and expand upon CTLA-4 blockade
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 observe...
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2023-12-01
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| Series: | OncoImmunology |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/2162402X.2023.2246319 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Sabrina N. Bossio |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-c2c7022bc10c4d4d97766bb302e5a761 |
| institution | DOAJ |
| issn | 2162-402X |
| language | English |
| publishDate | 2023-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | OncoImmunology |
| spelling | doaj-art-c2c7022bc10c4d4d97766bb302e5a7612025-08-20T02:50:44ZengTaylor & Francis GroupOncoImmunology2162-402X2023-12-0112110.1080/2162402X.2023.2246319CD39+ conventional CD4+ T cells with exhaustion traits and cytotoxic potential infiltrate tumors and expand upon CTLA-4 blockadeSabrina N. Bossio0Carolina Abrate1Jimena Tosello Boari2Constanza Rodriguez3Fernando P. Canale4María C. Ramello5Valentina Brunotto6Wilfrid Richer7Dario Rocha8Christine Sedlik9Anne Vincent-Salomon10Edith Borcoman11Andres Del Castillo12Adriana Gruppi13Elmer Fernandez14Eva V. Acosta Rodríguez15Eliane Piaggio16Carolina L. Montes17Departamento de Bioquímica Clínica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba, ArgentinaDepartamento de Bioquímica Clínica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba, ArgentinaInstitut Curie Research Center, Translational Research Department, INSERM U932, PSL Research University, Paris, FranceDepartamento de Bioquímica Clínica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba, ArgentinaDepartamento de Bioquímica Clínica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba, ArgentinaDepartamento de Bioquímica Clínica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba, ArgentinaDepartamento de Bioquímica Clínica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba, ArgentinaInstitut Curie Research Center, Translational Research Department, INSERM U932, PSL Research University, Paris, FranceCentro de Investigación y desarrollo en inmunología y enfermedades infecciosas (CIDIE-CONICET), ArgentinaInstitut Curie Research Center, Translational Research Department, INSERM U932, PSL Research University, Paris, FranceDiagnostic and Theranostic Medicine Division, Institut Curie, PSL Research University, Paris, FranceDepartment of Medical Oncology, Institut Curie, Paris, FranceHospital Rawson, Polo Sanitario, Córdoba, ArgentinaDepartamento de Bioquímica Clínica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba, ArgentinaCentro de Investigación y desarrollo en inmunología y enfermedades infecciosas (CIDIE-CONICET), ArgentinaDepartamento de Bioquímica Clínica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba, ArgentinaInstitut Curie Research Center, Translational Research Department, INSERM U932, PSL Research University, Paris, FranceDepartamento de Bioquímica Clínica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba, ArgentinaConventional 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.https://www.tandfonline.com/doi/10.1080/2162402X.2023.2246319CancerCD39conventional CD4+ T cellscytotoxicityexhaustion |
| spellingShingle | 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 CD39+ conventional CD4+ T cells with exhaustion traits and cytotoxic potential infiltrate tumors and expand upon CTLA-4 blockade OncoImmunology Cancer CD39 conventional CD4+ T cells cytotoxicity exhaustion |
| title | CD39+ conventional CD4+ T cells with exhaustion traits and cytotoxic potential infiltrate tumors and expand upon CTLA-4 blockade |
| title_full | CD39+ conventional CD4+ T cells with exhaustion traits and cytotoxic potential infiltrate tumors and expand upon CTLA-4 blockade |
| title_fullStr | CD39+ conventional CD4+ T cells with exhaustion traits and cytotoxic potential infiltrate tumors and expand upon CTLA-4 blockade |
| title_full_unstemmed | CD39+ conventional CD4+ T cells with exhaustion traits and cytotoxic potential infiltrate tumors and expand upon CTLA-4 blockade |
| title_short | CD39+ conventional CD4+ T cells with exhaustion traits and cytotoxic potential infiltrate tumors and expand upon CTLA-4 blockade |
| title_sort | cd39 conventional cd4 t cells with exhaustion traits and cytotoxic potential infiltrate tumors and expand upon ctla 4 blockade |
| topic | Cancer CD39 conventional CD4+ T cells cytotoxicity exhaustion |
| url | https://www.tandfonline.com/doi/10.1080/2162402X.2023.2246319 |
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