Targeting NKG2A to boost anti-tumor CD8 T-cell responses in human colorectal cancer.

Autor:	Ducoin K; Nantes Université, Univ Angers, INSERM, Immunology and New Concepts in ImmunoTherapy, INCIT, UMR 1302. F-44000 Nantes, France.; LabEx IGO, Université de Nantes, Nantes, France., Oger R; LabEx IGO, Université de Nantes, Nantes, France.; Université de Nantes, INSERM, CRCINA, F-44000 Nantes, France., Bilonda Mutala L; LabEx IGO, Université de Nantes, Nantes, France.; Université de Nantes, INSERM, CRCINA, F-44000 Nantes, France.; Institut Roche, Boulogne-Billancourt, France., Deleine C; Nantes Université, Univ Angers, INSERM, Immunology and New Concepts in ImmunoTherapy, INCIT, UMR 1302. F-44000 Nantes, France.; LabEx IGO, Université de Nantes, Nantes, France., Jouand N; Université de Nantes, CHU Nantes, Inserm, CNRS, SFR Santé, Inserm UMS 016, CNRS UMS 3556, F-44000 Nantes, France., Desfrançois J; Université de Nantes, CHU Nantes, Inserm, CNRS, SFR Santé, Inserm UMS 016, CNRS UMS 3556, F-44000 Nantes, France., Podevin J; CHU Nantes, Department of Digestive Surgery and IMAD, Nantes, France., Duchalais E; CHU Nantes, Department of Digestive Surgery and IMAD, Nantes, France., Cruard J; Université de Nantes, INSERM, CRCINA, F-44000 Nantes, France., Benlalam H; Nantes Université, Univ Angers, INSERM, Immunology and New Concepts in ImmunoTherapy, INCIT, UMR 1302. F-44000 Nantes, France.; LabEx IGO, Université de Nantes, Nantes, France., Labarrière N; Nantes Université, Univ Angers, INSERM, Immunology and New Concepts in ImmunoTherapy, INCIT, UMR 1302. F-44000 Nantes, France.; LabEx IGO, Université de Nantes, Nantes, France., Bossard C; LabEx IGO, Université de Nantes, Nantes, France.; Université de Nantes, INSERM, CRCINA, F-44000 Nantes, France.; CHU Nantes, Department of Digestive Surgery and IMAD, Nantes, France., Jarry A; Nantes Université, Univ Angers, INSERM, Immunology and New Concepts in ImmunoTherapy, INCIT, UMR 1302. F-44000 Nantes, France.; LabEx IGO, Université de Nantes, Nantes, France., Gervois-Segain N; Nantes Université, Univ Angers, INSERM, Immunology and New Concepts in ImmunoTherapy, INCIT, UMR 1302. F-44000 Nantes, France.; LabEx IGO, Université de Nantes, Nantes, France.
Jazyk:	angličtina
Zdroj:	Oncoimmunology [Oncoimmunology] 2022 Mar 09; Vol. 11 (1), pp. 2046931. Date of Electronic Publication: 2022 Mar 09 (Print Publication: 2022).
DOI:	10.1080/2162402X.2022.2046931
Abstrakt:	Recently, the inhibitory CD94/NKG2A receptor has joined the group of immune checkpoints (ICs) and its expression has been documented in NK cells and CD8 + T lymphocytes in several cancers and some infectious diseases. In colorectal cancer (CRC), we previously reported that NKG2A + tumor-infiltrating lymphocytes (TILs) are predominantly CD8 + αβ T cells and that CD94 overexpression and/or its ligand HLA-E were associated with a poor prognosis. This study aimed to thoroughly characterize the NKG2A + CD8 + TIL subpopulation and document the impact of NKG2A on anti-tumor responses in CRC. Our findings highlight new features of this subpopulation: (i) enrichment in colorectal tumors compared to paired normal colonic mucosa, (ii) their character as tissue-resident T cells and their majority terminal exhaustion status, (iii) co-expression of other ICs delineating two subgroups differing mainly in the level of NKG2A expression and the presence of PD-1, (iv) high functional avidity despite reduced proliferative capacity and finally (v) inhibition of anti-tumor reactivity that is overcome by blocking NKG2A. From a clinical point of view, these results open a promising alternative for immunotherapies based on NKG2A blockade in CRC, which could be performed alone or in combination with other IC inhibitors, adoptive cell transfer or therapeutic vaccination. Competing Interests: No potential conflict of interest was reported by the author(s). (© 2022 The Author(s). Published with license by Taylor & Francis Group, LLC.)
Databáze:	MEDLINE
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