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

Pancreatic cancer has the worst prognosis of any human malignancy lymphocytes infiltration appears to be a major prognostic marker of the disease. There is a need to better characterise T-cells in pancreatic cancer to identify novel therapeutic strategies and stratify patients for current treatments. In this study, a multi-parameter analysis of eight human pancreatic cancer patients revealed novel characteristics of T-cells. Regulatory T-cell populations were characterized by a highly immunosuppressive states with high TIGIT and ICOS expression, and CD8 T-cells were either senescent or exhausted but with lower PD1 levels. These findings have been subsequently validated in a larger pancreatic cancer single-cell RNA sequencing dataset. These data suggest that the microenvironment of pancreatic cancer is extremely suppressive and could be a major driver of poor prognosis. This work identifies potential therapeutic targets and avenues that should be further investigated through rational design of clinical trials.