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Author Notes:

Correspondence: elizerm_vanallen@dfci.harvard.edu (E.M.V.A.), sramachandran@brown.edu (S.R.)

Conceptualization, S.R., S.S., and E.M.V.A.; Methodology, S.H.A., A.G., M.X.H., M.A.R., and S.S.; Formal Analysis, M.X.H., M.A.R., and S.S.; Writing, S.R., M.A.R., S.S., and E.M.V.A.; Supervision, S.R. and E.M.V.A.

We thank the patients who contributed to the TCGA study. The results published here are based upon data generated by the TCGA Research Network.

Disclosures: 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.

Subjects:

Research Funding:

he study was supported by the following funding sources: NSF CAREER DBI-1452622 (S.R.); NIH R01 GM118652 (S.R.); NIH U01 CA217875 (M.A.R.); Brown University Sidney Frank Fellowship (S.S.); PCF-V Foundation Challenge Award (E.M.V.A.); NIH R01 CA227388 (E.M.V.A.); and NIH U01 CA233100 (E.M.V.A.).

Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Cell Biology
  • Genome wide association
  • Common variants
  • CTLA-4 Blockade
  • PD-1 Blockade
  • DNA-Damage
  • Risk loci
  • Landscape
  • Gene
  • Complex
  • Cells

Germline Features Associated with Immune Infiltration in Solid Tumors

Journal Title:

Cell Reports

Volume:

Volume 30, Number 9

Publisher:

, Pages 2900-+

Type of Work:

Article | Final Publisher PDF

Abstract:

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.

Copyright information:

© 2020 The Author(s).

This is an Open Access work distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (https://creativecommons.org/licenses/by-nc-nd/4.0/).
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