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.

NKG2A expression identifies a subset of human Vδ2 T cells exerting the highest antitumor effector functions / V. Cazzetta, E. Bruni, S. Terzoli, C. Carenza, S. Franzese, R. Piazza, P. Marzano, M. Donadon, G. Torzilli, M. Cimino, M. Simonelli, L. Bello, A. Villa, L. Tan, S. Ravens, I. Prinz, D. Supino, F.S. Colombo, E. Lugli, E. Marcenaro, E. Vivier, S. Della Bella, J. Mikulak, D. Mavilio. - In: CELL REPORTS. - ISSN 2211-1247. - 37:3(2021), pp. 109871.1-109871.23. [10.1016/j.celrep.2021.109871]

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

V. Cazzetta
Primo
;
E. Bruni;C. Carenza;S. Franzese;M. Donadon;G. Torzilli;M. Cimino;M. Simonelli;L. Bello;F.S. Colombo;S. Della Bella;J. Mikulak;D. Mavilio
Ultimo
2021

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.
cancer; cancer immune-therapy; hyper-reactivity; immune education; NKG2A immune checkpoint; Vδ2 T cells
Settore MED/46 - Scienze Tecniche di Medicina di Laboratorio
Settore MED/04 - Patologia Generale
Settore MED/50 - Scienze Tecniche Mediche Applicate
Settore MED/06 - Oncologia Medica
Settore MED/27 - Neurochirurgia
Settore MED/18 - Chirurgia Generale
Article (author)
File in questo prodotto:
File Dimensione Formato  
1-s2.0-S2211124721013383-main.pdf

accesso aperto

Tipologia: Publisher's version/PDF
Dimensione 4.8 MB
Formato Adobe PDF
4.8 MB Adobe PDF Visualizza/Apri
Pubblicazioni consigliate

Caricamento pubblicazioni consigliate

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/898751
Citazioni
  • ???jsp.display-item.citation.pmc??? 2
  • Scopus 3
  • ???jsp.display-item.citation.isi??? 5
social impact