期刊
CANCER DISCOVERY
卷 7, 期 10, 页码 1088-1097出版社
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/2159-8290.CD-17-0256
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资金
- MD Anderson Lung Cancer Moon Shot Program
- MD Anderson Physician Scientist Program
- Conquer Cancer Foundation Young Investigator Award
- Khalifa Scholar Award
- NIH CCSG Award [CA016672]
- Cancer Prevention and Research Institute of Texas [R120501]
- Cancer Prevention and Research Institute of Texas Multi-Investigator Research Award grant [RP160668]
- University of Texas (UT) Systems Stars Award [PS100149]
- Welch Foundation Robert A. Welch Distinguished University Chair Award [G-0040]
- Department of Defense PROSPECT grant [W81XWH-07-1-0306]
- UT Lung Specialized Programs of Research Excellence Grant [P50CA70907]
- MD Anderson Cancer Center Support Grant [CA016672]
- T.J. Martell Foundation
- Kimberley Clarke Foundation Award for Scientific Achievement through MD Anderson's Odyssey Fellowship Program
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 (C) 2017 AACR.
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