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

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; FS Colombo; E Lugli; E Marcenaro; E Vivier; S Della Bella; J Mikulak; D Mavilio

doi:10.1016/j.celrep.2021.109871

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

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, FS Colombo, E Lugli, E MarcenaroE Vivier, S Della Bella, J Mikulak, D Mavilio

Research output: Contribution to journal › Article › peer-review

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. © 2021 The Author(s)

Original language	English
Article number	109871
Journal	Cell Reports
Volume	37
Issue number	3
DOIs	https://doi.org/10.1016/j.celrep.2021.109871
Publication status	Published - 2021

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Cazzetta, V., Bruni, E., Terzoli, S., Carenza, C., Franzese, S., Piazza, R., Marzano, P., Donadon, M., Torzilli, G., Cimino, M., Simonelli, M., Bello, L., Villa, A., Tan, L., Ravens, S., Prinz, I., Supino, D., Colombo, FS., Lugli, E., ... Mavilio, D. (2021). NKG2A expression identifies a subset of human Vδ2 T cells exerting the highest antitumor effector functions: Cell Reports. Cell Reports, 37(3), [109871]. https://doi.org/10.1016/j.celrep.2021.109871

Cazzetta, V, Bruni, E, Terzoli, S, Carenza, C, Franzese, S, Piazza, R, Marzano, P, Donadon, M , Torzilli, G , Cimino, M, Simonelli, M, Bello, L, Villa, A, Tan, L, Ravens, S, Prinz, I, Supino, D, Colombo, FS , Lugli, E, Marcenaro, E, Vivier, E, Della Bella, S, Mikulak, J & Mavilio, D 2021, 'NKG2A expression identifies a subset of human Vδ2 T cells exerting the highest antitumor effector functions: Cell Reports', Cell Reports, vol. 37, no. 3, 109871. https://doi.org/10.1016/j.celrep.2021.109871

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title = "NKG2A expression identifies a subset of human Vδ2 T cells exerting the highest antitumor effector functions: Cell Reports",

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{\textquoteright} overall survival. These findings open avenues for developing combined cellular and immunologic anticancer therapies. {\textcopyright} 2021 The Author(s)",

author = "V Cazzetta and E Bruni and S Terzoli and C Carenza and S Franzese and R Piazza and P Marzano and M Donadon and G Torzilli and M Cimino and M Simonelli and L Bello and A Villa and L Tan and S Ravens and I Prinz and D Supino and FS Colombo and E Lugli and E Marcenaro and E Vivier and {Della Bella}, S and J Mikulak and D Mavilio",

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AU - Cazzetta, V

AU - Bruni, E

AU - Terzoli, S

AU - Carenza, C

AU - Franzese, S

AU - Piazza, R

AU - Marzano, P

AU - Donadon, M

AU - Torzilli, G

AU - Cimino, M

AU - Simonelli, M

AU - Bello, L

AU - Villa, A

AU - Tan, L

AU - Ravens, S

AU - Prinz, I

AU - Supino, D

AU - Colombo, FS

AU - Lugli, E

AU - Marcenaro, E

AU - Vivier, E

AU - Della Bella, S

AU - Mikulak, J

AU - Mavilio, D

PY - 2021

Y1 - 2021

N2 - 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. © 2021 The Author(s)

AB - 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. © 2021 The Author(s)

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DO - 10.1016/j.celrep.2021.109871

M3 - Article

SN - 2211-1247

VL - 37

JO - Cell Reports

JF - Cell Reports

IS - 3

M1 - 109871

ER -

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

Abstract

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