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

Valentina Cazzetta; Elena Bruni; Sara Terzoli; Claudia Carenza; Sara Franzese; Rocco Piazza; Paolo Marzano; Matteo Donadon; Guido Torzilli; Matteo Cimino; Matteo Simonelli; Lorenzo Bello; Anna Villa; Likai Tan; Sarina Ravens; Immo Prinz; Domenico Supino; Federico S. Colombo; Enrico Lugli; Emanuela Marcenaro; Eric Vivier; Silvia Della Bella; Joanna Mikulak; Domenico Mavilio

doi:10.1016/j.celrep.2021.109871

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

Valentina Cazzetta, Elena Bruni, Sara Terzoli, Claudia Carenza, Sara Franzese, Rocco Piazza, Paolo Marzano, Matteo Donadon, Guido Torzilli, Matteo Cimino, Matteo Simonelli, Lorenzo Bello, Anna Villa, Likai Tan, Sarina Ravens, Immo Prinz, Domenico Supino, Federico S. Colombo, Enrico Lugli, Emanuela MarcenaroEric Vivier, Silvia Della Bella, Joanna Mikulak, Domenico Mavilio

Risultato della ricerca: Contributo su rivista › Articolo in rivista › 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.

Lingua originale	Inglese
Numero di articolo	109871
Rivista	Cell Reports
Volume	37
Numero di pubblicazione	3
DOI	https://doi.org/10.1016/j.celrep.2021.109871
Stato di pubblicazione	Pubblicato - 19 ott 2021
Pubblicato esternamente	Sì

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10.1016/j.celrep.2021.109871

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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, F. S., Lugli, E., ... Mavilio, D. (2021). NKG2A expression identifies a subset of human Vδ2 T cells exerting the highest antitumor effector functions. Cell Reports, 37(3), Articolo 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",

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.",

keywords = "NKG2A immune checkpoint, Vδ2 T cells, cancer, cancer immune-therapy, hyper-reactivity, immune education",

author = "Valentina Cazzetta and Elena Bruni and Sara Terzoli and Claudia Carenza and Sara Franzese and Rocco Piazza and Paolo Marzano and Matteo Donadon and Guido Torzilli and Matteo Cimino and Matteo Simonelli and Lorenzo Bello and Anna Villa and Likai Tan and Sarina Ravens and Immo Prinz and Domenico Supino and Colombo, \{Federico S.\} and Enrico Lugli and Emanuela Marcenaro and Eric Vivier and \{Della Bella\}, Silvia and Joanna Mikulak and Domenico Mavilio",

note = "Publisher Copyright: {\textcopyright} 2021 The Author(s)",

year = "2021",

month = oct,

day = "19",

doi = "10.1016/j.celrep.2021.109871",

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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, 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, vol. 37, n. 3, 109871. https://doi.org/10.1016/j.celrep.2021.109871

TY - JOUR

T1 - NKG2A expression identifies a subset of human Vδ2 T cells exerting the highest antitumor effector functions

AU - Cazzetta, Valentina

AU - Bruni, Elena

AU - Terzoli, Sara

AU - Carenza, Claudia

AU - Franzese, Sara

AU - Piazza, Rocco

AU - Marzano, Paolo

AU - Donadon, Matteo

AU - Torzilli, Guido

AU - Cimino, Matteo

AU - Simonelli, Matteo

AU - Bello, Lorenzo

AU - Villa, Anna

AU - Tan, Likai

AU - Ravens, Sarina

AU - Prinz, Immo

AU - Supino, Domenico

AU - Colombo, Federico S.

AU - Lugli, Enrico

AU - Marcenaro, Emanuela

AU - Vivier, Eric

AU - Della Bella, Silvia

AU - Mikulak, Joanna

AU - Mavilio, Domenico

PY - 2021/10/19

Y1 - 2021/10/19

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.

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.

KW - NKG2A immune checkpoint

KW - Vδ2 T cells

KW - cancer

KW - cancer immune-therapy

KW - hyper-reactivity

KW - immune education

UR - http://www.scopus.com/inward/record.url?scp=85119952705&partnerID=8YFLogxK

U2 - 10.1016/j.celrep.2021.109871

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

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