Targeting NKG2A to boost anti-tumor CD8 T-cell responses in human colorectal cancer. (31st December 2022)

• Record Type: Journal Article
• Authors: Ducoin, Kathleen; Oger, Romain; Bilonda Mutala, Linda; Deleine, Cécile; Jouand, Nicolas; Desfrançois, Juliette; Podevin, Juliette; Duchalais, Emilie; Cruard, Jonathan; Benlalam, Houssem; Labarrière, Nathalie; Bossard, Céline; Jarry, Anne; Gervois-Segain, Nadine
• Is Part Of: Oncoimmunology. Volume 11:Number 1(2022)
• Publication Date: 2022-12-31
• Subjects: NKG2A -- CD8+ TILs -- colorectal cancer -- immune checkpoint inhibitor; Tumors -- Immunological aspects -- Periodicals; Neoplasms -- therapy -- Periodicals; Immunotherapy -- Periodicals; 616.994
• DOI: 10.1080/2162402X.2022.2046931
• Languages: English
• ISSNs: 2162-402X

Abstract

Abstract: 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. Graphical Abstract: uf0001