Immune responses in pancreatic cancer may be restricted by prevalence of activated regulatory T-cells, dysfunctional CD8+ T-cells, and senescent T-cells [article]

Shivan Sivakumar, Enas Abu-Shah, David Ahern, Edward H Arbe-Barnes, Nagina Mangal, Srikanth Reddy, Aniko Rendek, Alistair Easton, Elke Kurz, Michael Silva, Lara R Heij, Zahir Soonawalla (+3 others)
2020 bioRxiv   pre-print
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
more » ... 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.
doi:10.1101/2020.06.20.163071 fatcat:r4e72d7qd5dyjk3hy6y5bo5kka