Association of Germline Variants in Natural Killer Cells With Tumor Immune Microenvironment Subtypes, Tumor-Infiltrating Lymphocytes, Immunotherapy Response, Clinical Outcomes, and Cancer Risk

Key Points Question Are germline variants of natural killer (NK) cells associated with tumor immune microenvironment subtypes, cancer risk, prognosis, and immunotherapy? Findings This genetic association study analyzed functionally mutated genes in the germline genomes of 5883 patients with 13 common cancers and 4500 individuals with no cancer, finding that the number of functionally mutated genes in NK cell germlines was negatively associated with the abundance of tumor-infiltrating lymphocytes, clinical outcomes, and immunotherapy response but positively associated with cancer risk. Meaning Findings suggest that germline genetic variants in NK cells could help to identify individuals at risk of cancer and to improve existing immune checkpoint and chimeric antigen receptor–T cell therapies by adoptive transfer of healthy NK cells.

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