Single cell transcriptomic and T cell repertoire analysis reveals trajectory of tumor - infiltrating lymphocyte states in pancreatic cancer

The CD8+ TIL contained a putative transitional GZMK+ population based on TCR clonotype sharing, and cell-state trajectory analysis showed similarity to a GZMB+PRF1+ cytotoxic and a CXCL13+ dysfunctional population. Statistical analysis suggested that certain TIL states, such as dysfunctional and inhibitory populations, often occurred together. Finally, analysis of cultured TIL revealed that high-frequency clones from effector populations were preferentially expanded. These data provide a framework for understanding the PDAC TIL landscape for future TIL use in immunotherapy for PDAC. we profiled 80,000 T cells from 57 PDAC, 22 uninvolved/normal samples, and cultured TIL using single-cell transcriptomic and T-cell receptor analysis.