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Publication : NKG7 Is Required for Optimal Antitumor T-cell Immunity.

First Author  Li XY Year  2022
Journal  Cancer Immunol Res Volume  10
Issue  2 Pages  154-161
PubMed ID  35013002 Mgi Jnum  J:376304
Mgi Id  MGI:8269074 Doi  10.1158/2326-6066.CIR-20-0649
Citation  Li XY, et al. (2022) NKG7 Is Required for Optimal Antitumor T-cell Immunity. Cancer Immunol Res 10(2):154-161
abstractText  Tumor antigen-specific CD8(+) T cells play a critical role in antitumor immunity. Clinical trials reinvigorating the immune system via immune checkpoint blockade (ICB) have shown remarkable clinical promise. Numerous studies have identified an association between NKG7 expression and patient outcome across different malignancies. However, aside from these correlative observations, very little is known about NKG7 and its role in antitumor immunity. Herein, we utilized single-cell RNA sequencing (scRNA-seq) datasets, NKG7-deficient mice, NKG7-reporter mice, and mouse tumor models to investigate the role of NKG7 in neoantigen-mediated tumor rejection and ICB immunotherapy. scRNA-seq of tumors from patients with metastatic melanoma or head and neck squamous cell carcinoma revealed that NKG7 expression is highly associated with cytotoxicity and specifically expressed by CD8(+) T cells and natural killer (NK) cells. Furthermore, we identified a key role for NKG7 in controlling intratumor T-cell accumulation and activation. NKG7 was upregulated on intratumor antigen-specific CD8(+) T cells and NK cells and required for the accumulation of T cells in the tumor microenvironment. Accordingly, neoantigen-expressing mouse tumors grew faster in Nkg7-deficient mice. Strikingly, efficacy of single or combination ICB was significantly reduced in Nkg7-deficient mice.See related article by Wen et al., p. 162.
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