Student and Faculty Publications
Publication Date
10-5-2022
Journal
Cancer Discovery
Abstract
Pancreatic ductal adenocarcinoma (PDAC) has few effective treatments. Immunotherapy, an attractive alternative strategy, remains challenging with the lack of knowledge on the tumor-infiltrating lymphocyte (TIL) landscape in PDAC. To generate a reference of T-cell subpopulations, we profiled 80,000 T cells from 57 PDAC samples, 22 uninvolved/normal samples, and cultured TIL using single-cell transcriptomic and T-cell receptor analysis. These data revealed 20 cell states and heterogeneous distributions of TIL populations. The CD8+ TIL contained a putative transitional GZMK+ population based on T-cell receptor 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.
Keywords
Carcinoma, Pancreatic Ductal, Humans, Lymphocytes, Tumor-Infiltrating, Pancreatic Neoplasms, Receptors, Antigen, T-Cell
Included in
Bioinformatics Commons, Biomedical Informatics Commons, Digestive System Diseases Commons, Gastroenterology Commons, Medical Sciences Commons, Oncology Commons
Comments
Supplementary Materials
PMID: 35849783