1. TCR Repertoire Intratumor Heterogeneity in Localized Lung Adenocarcinomas: An Association with Predicted Neoantigen Heterogeneity and Postsurgical Recurrence
- Author
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Tina Cascone, P. Andrew Futreal, Chang-Jiun Wu, Lorenzo Federico, J. Jack Lee, Ignacio I. Wistuba, Harlan Robins, John V. Heymach, Carmen Behrens, Chantale Bernatchez, Alexandre Reuben, Runzhe Chen, Stephen G. Swisher, Jennifer A. Wargo, Rachel M. Gittelman, Jianhua Zhang, Marissa Vignali, Boris Sepesi, Latasha Little, Marie Andrée Forget, Jianjun Zhang, Jaime Rodriguez-Canales, Ryan O. Emerson, Erik Yusko, Vancheswaran Gopalakrishnan, Jianjun Gao, Kelly Quek, Luis M Vence, Sharon Benzeno, William N. William, Don L. Gibbons, Cara Haymaker, Jun Li, Padmanee Sharma, Christopher M. Tipton, Junya Fujimoto, James P. Allison, Edwin Roger Parra, Curtis Gumbs, and Jiexin Zhang
- Subjects
0301 basic medicine ,Lung Neoplasms ,Receptors, Antigen, T-Cell ,Adenocarcinoma of Lung ,Adenocarcinoma ,Biology ,medicine.disease_cause ,Article ,Disease-Free Survival ,Genetic Heterogeneity ,03 medical and health sciences ,0302 clinical medicine ,Antigen ,Carcinoma, Non-Small-Cell Lung ,Exome Sequencing ,medicine ,Carcinoma ,Humans ,Clinical significance ,Mutation ,Genetic heterogeneity ,Repertoire ,Histocompatibility Antigens Class I ,T-cell receptor ,Histocompatibility Antigens Class II ,Cancer ,medicine.disease ,Gene Expression Regulation, Neoplastic ,030104 developmental biology ,Oncology ,030220 oncology & carcinogenesis ,Immunology ,Neoplasm Recurrence, Local - 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. Cancer Discov; 7(10); 1088–97. ©2017 AACR. This article is highlighted in the In This Issue feature, p. 1047
- Published
- 2017
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