Germline Features Associated with Immune Infiltration in Solid Tumors.

The immune composition of the tumor microenvironment influences response and resistance to immunotherapies. While numerous studies have identified somatic correlates of immune infiltration, germline features that associate with immune infiltrates in cancers remain incompletely characterized. We analyze seven million autosomal germline variants in the TCGA cohort and test for association with established immune-related phenotypes that describe the tumor immune microenvironment. We identify one SNP associated with the amount of infiltrating follicular helper T cells; 23 candidate genes, some of which are involved in cytokine-mediated signaling and others containing cancer-risk SNPs; and networks with genes that are part of the DNA repair and transcription elongation pathways. In addition, we find a positive association between polygenic risk for rheumatoid arthritis and amount of infiltrating CD8 ⁺ T cells. Overall, we identify multiple germline genetic features associated with tumor-immune phenotypes and develop a framework for probing inherited features that contribute to differences in immune infiltration.
Competing Interests: Declaration of Interests E.M.V.A. serves in an advisory/consulting role for the following corporations: Tango Therapeutics, Genome Medical, Invitae, Illumina, Ervaxx, and Janssen. He receives research support from Novartis and Bristol-Myers Squibb. He owns equity in Tango Therapeutics, Genome Medical, Syapse, Microsoft, and Ervaxx. He has received travel reimbursement from Roche/Genentech. He holds institutional patents filed on ERCC2 mutations and chemotherapy response, chromatin mutations and immunotherapy response, and methods for clinical interpretation.
(Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.)