Abstract
Genomic intratumor heterogeneity (ITH) may be associated with postsurgical relapse of localized lung adenocarcinomas. Recently, mutations, through generation of neoantigens, were shown to alter tumor immunogenicity through T-cell responses. Here, we performed sequencing of the T-cell receptor (TCR) in 45 tumor regions from 11 localized lung adenocarcinomas and observed substantial intratumor differences in T-cell density and clonality with the majority of T-cell clones restricted to individual tumor regions. TCR ITH positively correlated with predicted neoantigen ITH, suggesting that spatial differences in the T-cell repertoire may be driven by distinct neoantigens in different tumor regions. Finally, a higher degree of TCR ITH was associated with an increased risk of postsurgical relapse and shorter disease-free survival, suggesting a potential clinical significance of T-cell repertoire heterogeneity. SIGNIFICANCE: The present study provides insights into the ITH of the T-cell repertoire in localized lung adenocarcinomas and its potential biological and clinical impact. The results suggest that T-cell repertoire ITH may be tightly associated to genomic ITH and disease relapse.
Original language | English (US) |
---|---|
Pages (from-to) | 1088-1097 |
Number of pages | 10 |
Journal | Cancer Discovery |
Volume | 7 |
Issue number | 10 |
DOIs | |
State | Published - Oct 1 2017 |
ASJC Scopus subject areas
- Oncology
MD Anderson CCSG core facilities
- Bioinformatics Shared Resource
- Biostatistics Resource Group
- Tissue Biospecimen and Pathology Resource
- Clinical Trials Office