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

ABSTRACT: Importance:Only a small fraction of patients with cancer receiving immune checkpoint therapy (ICT) respond, which is associated with tumor immune microenvironment (TIME) subtypes and tumor-infiltrating lymphocytes (TILs). Objective:To examine whether germline variants of natural killer (NK) cells, a key component of the immune system, are associated with TIME subtypes, the abundance of TILs, response to ICT, clinical outcomes, and cancer risk. Design, Setting, and Participants:This genetic association study explored TIME subtypes and examined the association of the germline genomic information of patients with cancer with TIME subtypes, abundance of TILs, response to ICT, prognosis, and cancer risk. Clinical information, tumor RNA sequencing, and whole-exome sequencing (WES) data of paired normal samples of patients with 13 common cancers (n?=?5883) were obtained from the Cancer Genome Atlas. The WES data of individuals with no cancer (n?=?4500) were obtained from the database of Genotypes and Phenotypes. Data collection and analysis took place in March 2017. Main Outcomes and Measures:Associations between the number of germline defective genes in NK cells and survival time and the abundance of TILs. Results:Based on tumor RNA sequencing data, tumors were stratified into TIME-rich, TIME-intermediate, and TIME-poor subtypes. Tumors of TIME-rich subtype had more TILs (TIL-NK cells in TIME-rich head and neck squamous cell carcinoma [HNSC] tumors: t?=?4.85; 95% CI of the difference, 0.01-0.03; P?=?2.19?×?10-6) compared with TIME-intermediate HNSC tumors (t?=?3.70; 95% CI of the difference, 0.01-0.03; P?

SUBMITTER: Xu X 

PROVIDER: S-EPMC6727785 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature