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<jats:title>Abstract</jats:title><jats:p>Pancreatic cancer has the worst prognosis of any human malignancy and lymphocytes appear to be a major prognostic marker of the disease. There is a need to better characterise T-cells of pancreatic cancer in order to identify novel therapeutic strategies. In this study, a multi-parameter analysis of human pancreatic cancer cases revealed three novel characteristics of T-cells. Using a T-cell focused CyTOF panel, we analysed approximately 32,000 T-cells in eight patients. Our observations show a regulatory T-cell population was characterized by a highly immunosuppressive state with high TIGIT and ICOS expression, and the CD8 T-cells were either senescent or exhausted but with lower PD1 levels. These data suggest that the microenvironment of pancreatic cancer is extremely suppressive and could be a major driver of poor prognosis. These findings have been subsequently validated in a large pancreatic cancer single-cell RNA sequencing dataset using 13,000 T cells. This work identifies potential therapeutic targets and avenues that should be further investigated through rational design of clinical trials.</jats:p>

Original publication

DOI

10.1101/2020.06.20.163071

Type

Journal article

Publisher

Cold Spring Harbor Laboratory

Publication Date

21/06/2020