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NKG2A expression identifies a subset of human Vδ2 T cells exerting the highest antitumor effector functions

Abstract : Human Vδ2 cells are innate-like γδ T effectors performing potent immune surveillance against tumors. The constitutive expression of NKG2A identifies a subset of Vδ2 T cells licensed with an intrinsic hyper-responsiveness against cancer. Indeed, the transcriptomic profiles of NKG2A+ and NKG2A- cells characterize two distinct "intralineages" of Vδ2 T lymphocytes that appear early during development, keep their phenotypes, and show self-renewal capabilities in adult life. The hyper-responsiveness of NKG2A+ Vδ2 T cells is counterbalanced by the inhibitory signaling delivered by human leukocyte antigen E (HLA-E) expressed on malignant cells as a tumor-escape mechanism. However, either masking or knocking out NKG2A restores the capacity of Vδ2 T cells to exert the highest effector functions even against HLA-E+ tumors. This is highly relevant in the clinic, as the different degrees of engagement of the NKG2A-HLA-E checkpoint in hepatocellular carcinoma, glioblastoma, and non-small cell lung cancer directly impact patients' overall survival. These findings open avenues for developing combined cellular and immunologic anticancer therapies.
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https://hal-amu.archives-ouvertes.fr/hal-03566006
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Submitted on : Friday, February 11, 2022 - 12:18:38 PM
Last modification on : Thursday, December 1, 2022 - 9:12:21 AM

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Valentina Cazzetta, Elena Bruni, Sara Terzoli, Claudia Carenza, Sara Franzese, et al.. NKG2A expression identifies a subset of human Vδ2 T cells exerting the highest antitumor effector functions. Cell Reports, 2021, 37 (3), pp.109871. ⟨10.1016/j.celrep.2021.109871⟩. ⟨hal-03566006⟩

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