Data from NKG7 Is Required for Optimal Antitumor T-cell Immunity

Abstract

<div>Abstract<p>Tumor antigen-specific CD8<sup>+</sup> 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 <i>NKG7</i> 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, <i>NKG7</i>-deficient mice, <i>NKG7</i>-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 <i>NKG7</i> expression is highly associated with cytotoxicity and specifically expressed by CD8<sup>+</sup> 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<sup>+</sup> 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 <i>Nkg7</i>-deficient mice. Strikingly, efficacy of single or combination ICB was significantly reduced in <i>Nkg7</i>-deficient mice.</p><p><i><a href="https://aacrjournals.org/cancerimmunolres/article/10/2/162/678013/NKG7-Is-a-T-cell-Intrinsic-Therapeutic-Target-for" target="_blank">See related article by Wen et al., p. 162</a></i></p></div>