| 描述信息 |
Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal human cancers and has few effective treatments. Immunotherapy represents an attractive alternative treatment strategy but has shown little benefit against PDAC. Increased knowledge of the tumor-infiltrating lymphocyte (TIL) landscape in PDAC could lead to more efficacious immunotherapy. To generate a reference of T-cell subpopulations, we profiled 39,694 T cells from 57 PDAC samples and 22 uninvolved/normal samples, as well as 40,605 T cells from cultured TIL, using single-cell transcriptomic and T-cell receptor analysis. These data revealed 20 total cell states and heterogeneous distributions of TIL populations. The CD8+ TIL contained a putative transitional GZMK+ population based on TCR clonotype sharing, and cell-state trajectory analysis showed a high similarity to a GZMB+PRF1+ cytotoxic population and a CXCL13+ dysfunctional population. Furthermore, statistical analysis suggested that different TIL milieu profiles, such as dysfunctional and inhibitory populations, often occurred together in PDAC. Finally, analysis of cultured TIL revealed that high-frequency clones from activated effector populations were preferentially expanded. These data provide a framework for understanding the PDAC TIL landscape for future TIL use in cellular immunotherapy for PDAC. |
