CD39 + conventional CD4 + T cells with exhaustion traits and cytotoxic potential infiltrate tumors and expand upon CTLA-4 blockade.

Autor:	Bossio SN; Departamento de Bioquímica Clínica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba, Argentina.; Centro de Investigaciones en Bioquímica Clínica e Inmunología (CIBICI-CONICET), Córdoba, Argentina., Abrate C; Departamento de Bioquímica Clínica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba, Argentina.; Centro de Investigaciones en Bioquímica Clínica e Inmunología (CIBICI-CONICET), Córdoba, Argentina., Tosello Boari J; Institut Curie Research Center, Translational Research Department, INSERM U932, PSL Research University, Paris, France., Rodriguez C; Departamento de Bioquímica Clínica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba, Argentina.; Centro de Investigaciones en Bioquímica Clínica e Inmunología (CIBICI-CONICET), Córdoba, Argentina., Canale FP; Departamento de Bioquímica Clínica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba, Argentina.; Centro de Investigaciones en Bioquímica Clínica e Inmunología (CIBICI-CONICET), Córdoba, Argentina., Ramello MC; Departamento de Bioquímica Clínica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba, Argentina.; Centro de Investigaciones en Bioquímica Clínica e Inmunología (CIBICI-CONICET), Córdoba, Argentina., Brunotto V; Departamento de Bioquímica Clínica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba, Argentina.; Centro de Investigaciones en Bioquímica Clínica e Inmunología (CIBICI-CONICET), Córdoba, Argentina., Richer W; Institut Curie Research Center, Translational Research Department, INSERM U932, PSL Research University, Paris, France., Rocha D; Centro de Investigación y desarrollo en inmunología y enfermedades infecciosas (CIDIE-CONICET), Argentina., Sedlik C; Institut Curie Research Center, Translational Research Department, INSERM U932, PSL Research University, Paris, France., Vincent-Salomon A; Diagnostic and Theranostic Medicine Division, Institut Curie, PSL Research University, Paris, France., Borcoman E; Department of Medical Oncology, Institut Curie, Paris, France., Del Castillo A; Hospital Rawson, Polo Sanitario, Córdoba, Argentina., Gruppi A; Departamento de Bioquímica Clínica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba, Argentina.; Centro de Investigaciones en Bioquímica Clínica e Inmunología (CIBICI-CONICET), Córdoba, Argentina., Fernandez E; Centro de Investigación y desarrollo en inmunología y enfermedades infecciosas (CIDIE-CONICET), Argentina., Acosta Rodríguez EV; Departamento de Bioquímica Clínica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba, Argentina.; Centro de Investigaciones en Bioquímica Clínica e Inmunología (CIBICI-CONICET), Córdoba, Argentina., Piaggio E; Institut Curie Research Center, Translational Research Department, INSERM U932, PSL Research University, Paris, France., Montes CL; Departamento de Bioquímica Clínica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba, Argentina.; Centro de Investigaciones en Bioquímica Clínica e Inmunología (CIBICI-CONICET), Córdoba, Argentina.
Jazyk:	angličtina
Zdroj:	Oncoimmunology [Oncoimmunology] 2023 Aug 18; Vol. 12 (1), pp. 2246319. Date of Electronic Publication: 2023 Aug 18 (Print Publication: 2023).
DOI:	10.1080/2162402X.2023.2246319
Abstrakt:	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 γ , 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. Competing Interests: E.P. is co-founder of Egle-Tx. E.P. and J.T are consultants for Egle-Tx. The other authors declare no conflicts of interest. (© 2023 The Author(s). Published with license by Taylor & Francis Group, LLC.)
Databáze:	MEDLINE
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