Single-Cell Sequencing Reveals Trajectory of Tumor-Infiltrating Lymphocyte States in Pancreatic Cancer.
Journal
Cancer discovery
ISSN: 2159-8290
Titre abrégé: Cancer Discov
Pays: United States
ID NLM: 101561693
Informations de publication
Date de publication:
05 10 2022
05 10 2022
Historique:
received:
28
09
2021
revised:
09
05
2022
accepted:
14
07
2022
pubmed:
19
7
2022
medline:
7
10
2022
entrez:
18
7
2022
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 35849783
pii: 707058
doi: 10.1158/2159-8290.CD-21-1248
pmc: PMC9547957
mid: NIHMS1826134
doi:
Substances chimiques
Receptors, Antigen, T-Cell
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
2330-2349Subventions
Organisme : NCI NIH HHS
ID : R01 CA236864
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA016672
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA240526
Pays : United States
Organisme : NCI NIH HHS
ID : T32 CA009599
Pays : United States
Organisme : NCI NIH HHS
ID : K08 CA218690
Pays : United States
Informations de copyright
©2022 American Association for Cancer Research.
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