Local mutational diversity drives intratumoral immune heterogeneity in non-small cell lung cancer.
Combining whole exome sequencing, transcriptome profiling, and T cell repertoire analysis, we investigate the spatial features of surgically-removed biopsies from multiple loci in tumor masses of 15 patients with non-small cell lung cancer (NSCLC). This revealed that the immune microenvironment has high spatial heterogeneity such that intratumoral regional variation is as large as inter-personal variation. While the local total mutational burden (TMB) is associated with local T-cell clonal expansion, local anti-tumor cytotoxicity does not directly correlate with neoantigen abundance. Together, these findings caution against that immunological signatures can be predicted solely from TMB or microenvironmental analysis from a single locus biopsy.
Jia, Q; Wu, W; Wang, Y; Alexander, PB; Sun, C; Gong, Z; Cheng, J-N; Sun, H; Guan, Y; Xia, X; Yang, L; Yi, X; Wan, YY; Wang, H; He, J; Futreal, PA; Li, Q-J; Zhu, B
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