1. NKG2A expression identifies a subset of human Vδ2 T cells exerting the highest antitumor effector functions
- Author
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Cazzetta, Valentina, Bruni, Elena, Terzoli, Sara, Carenza, Claudia, Franzese, Sara, Piazza, Rocco, Marzano, Paolo, Donadon, Matteo, Torzilli, Guido, Cimino, Matteo, Simonelli, Matteo, Bello, Lorenzo, Villa, Anna, Tan, Likai, Ravens, Sarina, Prinz, Immo, Supino, Domenico, Colombo, Federico S., Lugli, Enrico, Marcenaro, Emanuela, Vivier, Eric, Della Bella, Silvia, Mikulak, Joanna, and Mavilio, Domenico
- 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.
- Published
- 2021
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