Therapeutic modulation of NKG7 in CD8+ T cells increases anti-tumor cytotoxicity and improves response to immune checkpoint inhibitors

Monoclonal antibodies that block PD-1/PD-L1 inhibitory signaling have been successfully used to treat a variety of solid tumor malignancies, but only a subset of patients benefit from this treatment. It remains unclear why the majority of patients fail to respond and what other limiting factors are at play. Here we show that natural killer cell granule protein-7 (NKG7) is critical for the anti-tumor activity of CD8+ T cells and response to anti-PD-1 therapy. We performed single-cell RNA sequencing analysis of peripheral CD8+ T cells from patients treated with anti-PD-1 and found that NKG7 gene expression was decreased in the non-responding patients. This study included a total of 8 individual patients; n=4 responders to anti-PD-1 therapy; n=4 non-responders to anti-PD-1 therapy. There are two representative samples from each patient, matching "BL" (baseline) and "PT" (12 weeks post initiation of treatment) timepoints. 8 samples also included VDJ library sequencing, as detailed in sample description below.