T cell receptor gene recombinations in human tumor specimen exome files: detection of T cell receptor-β VDJ recombinations associates with a favorable oncologic outcome for bladder cancer

Cancer Immunol Immunother. 2017 Mar;66(3):403-410. doi: 10.1007/s00262-016-1943-1. Epub 2016 Dec 19.

Abstract

Understanding tumor-resident T cells is important for cancer prognosis and treatment options. Conventional, solid tumor specimen exome files can be searched directly for recombined T cell receptor (TcR)-α segments; RNASeq files can include TcR-β VDJ recombinations. To learn whether there are medically relevant uses of exome-based detection of TcR V(D)J recombinations in the tumor microenvironment, we searched cancer genome atlas and Moffitt Cancer Center, tumor specimen exome files for TcR-β, TcR-γ, and TcR-δ recombinations, for bladder and stomach cancer. We found that bladder cancer exomes with productive TcR-β recombinations had a significant association with No Subsequent Tumors and a positive response to drug treatments, with p < 0.004, p < 0.05, and p < 0.004, depending on the sample sets examined. We also discovered the opportunity to detect productive TcR-γ and TcR-δ recombinations in the tumor microenvironment, via the tumor specimen exome files.

Keywords: Bladder cancer; Exome; Stomach cancer; T cell receptor recombination; TCGA; Tumor microenvironment.

MeSH terms

  • Exome
  • Genes, T-Cell Receptor beta
  • Genes, T-Cell Receptor*
  • Humans
  • Receptors, Antigen, T-Cell, alpha-beta / genetics*
  • Treatment Outcome
  • Tumor Microenvironment
  • Urinary Bladder Neoplasms / genetics*
  • V(D)J Recombination / genetics*

Substances

  • Receptors, Antigen, T-Cell, alpha-beta