TCR Repertoire Intratumor Heterogeneity in Localized Lung Adenocarcinomas: an Association with Predicted Neoantigen Heterogeneity and Postsurgical Recurrence [Research Briefs]

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.

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