73 Characterization of tumor-infiltrating T-cell repertoire in human cancers

Background TCR and BCR repertoire profiling is a promising technique that can provide clinically useful window into the complex interactions between tumor cells infiltrating lymphocytes. Despite recent advances in sequencing methods, characterization of tumor-infiltrating T-cell repertoires has been limited to small sample sizes due technical material constraints. In this study, we constructed large multidimensional database data covering diverse landscape HLA genotypes neoantigens from routine clinical sequencing. We present descriptive summary profiles derived tens thousands samples over fifty different cancer cohorts characterize associations various molecular features. Methods To enrich immune receptor transcripts detected by Tempus RNA-sequencing workflow, hybrid capture probes tiling genes were used. Repertoire reads aligned, assembled, annotated against IMGT reference sequences. Repertoires are profiled as component Tempus|xT RNA summarized here for >25 thousand 50 cohorts. Results demonstrate use TCR/BCR an effective method enriching without interfering with downstream transcriptomic analysis. These part larger, multimodal DNA/RNA-sequencing pipeline quantifies variety explored correlation high-level metrics like richness (the number unique clonotypes given repertoire) clonality/evenness (Shannon entropy) both gene expression-based (i.e. cell infiltration estimates, etc.) mutational patterns (mutational burden neoantigen load). Finally, observed clonality B-cell driven cancers frequently exhibits clear monoclonal dominance cells’ lymphoid receptors. Conclusions be incorporated high-volume generate dataset studying tumor-immune microenvironment. By creating large-scale tissue, genotypes, contexts, better resolve correlates host adaptive immunity.