posted on 2023-04-04, 00:21authored byAislyn Schalck, Donastas Sakellariou-Thompson, Marie-Andrée Forget, Emi Sei, Tara G. Hughes, Alexandre Reuben, Shanshan Bai, Min Hu, Tapsi Kumar, Mark W. Hurd, Matthew H.G. Katz, Ching-Wei D. Tzeng, Shubham Pant, Milind Javle, David R. Fogelman, Anirban Maitra, Cara L. Haymaker, Michael P. Kim, Nicholas E. Navin, Chantale Bernatchez
Supplementary Figure from Single-Cell Sequencing Reveals Trajectory of Tumor-Infiltrating Lymphocyte States in Pancreatic Cancer
Funding
National Cancer Institute (NCI)
United States Department of Health and Human Services
Cancer Prevention and Research Institute of Texas (CPRIT)
National Institutes of Health (NIH)
History
ARTICLE 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.
To improve the efficacy of immunotherapy in PDAC, there is a great need to understand the PDAC TIL landscape. This study represents a reference of PDAC TIL subpopulations and their relationships and provides a foundation upon which to base future immunotherapeutic efforts.This article is highlighted in the In This Issue feature, p. 2221