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Activated Regulatory T-Cells, Dysfunctional and Senescent T-Cells Hinder the Immunity in Pancreatic Cancer by Sivakumar, Shivan (author);Abu-Shah, Enas (author);Ahern, David J. (author);Arbe-Barnes, Edward H. (author);Jainarayanan, Ashwin K. (author);Mangal, Nagina (author);Reddy, Srikanth (author);Rendek, Aniko (author);Easton, Alistair (author);Kurz, Elke (author);Silva, Michael (author);Soonawalla, Zahir (author);Heij, Lara R. (author);Bashford-Rogers, Rachael (author);Middleton, Mark R. (author);Dustin, Michael L. (author) is a Medicine article available to read on EtoBox.

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## Simple Summary Pancreatic cancer has the worst survival of any human cancer. Checkpoint blockade has not yielded much benefit in pancreatic cancer. We explored immune cell phenotypes with this disease to identify new targets for checkpoint blockade therapy. We created a checkpoint-focused panel to analyse immune cells from eight pancreatic cancer patients. This showed us the majority of T-cells are senescent. Further T-cell investigation demonstrated the majority of cytotoxic T-cells have intermediate to low PD1 expression suggesting why PD1 may not work as a pancreatic cancer therapy strategy. Our data has also highlighted a regulatory T-cell population which is highly activated and can mediate immunosuppression. The checkpoints that are highly expressed on these cells are TIGIT, ICOS and CD39, suggesting inhibition of these may be a viable therapeutic strategy. Furthermore, we showed that Tregs were retained amongst the fibroblast stroma of the tumour. Our work suggests there are key checkpoints on Tregs that may help guide therapeutic strategies in pancreatic cancer. ## Abstract Pancreatic cancer has one of the worst prognoses of any human malignancy and leukocyte infiltratio

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Author

Sivakumar, Shivan (author);Abu-Shah, Enas (author);Ahern, David J. (author);Arbe-Barnes, Edward H. (author);Jainarayanan, Ashwin K. (author);Mangal, Nagina (author);Reddy, Srikanth (author);Rendek, Aniko (author);Easton, Alistair (author);Kurz, Elke (author);Silva, Michael (author);Soonawalla, Zahir (author);Heij, Lara R. (author);Bashford-Rogers, Rachael (author);Middleton, Mark R. (author);Dustin, Michael L. (author)

Publisher

MDPI AG

Published

2021

Language

EN

Field

Medicine (Health Sciences)