NKG2A expression identifies a subset of human Vδ2 T cells exerting the highest antitumor effector functions.
Cell Rep
; 37(3): 109871, 2021 10 19.
Article
em En
| MEDLINE
| ID: mdl-34686325
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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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Ativação Linfocitária
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Linfócitos do Interstício Tumoral
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Receptores de Antígenos de Linfócitos T gama-delta
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Citotoxicidade Imunológica
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Subfamília C de Receptores Semelhantes a Lectina de Células NK
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Linfócitos Intraepiteliais
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Neoplasias
Tipo de estudo:
Observational_studies
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Prognostic_studies
Limite:
Aged
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Female
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Humans
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Infant
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Male
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Middle aged
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article