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Expression of the metabolite transporter SLC4A4 in pancreatic cancer cells promotes immuneescape and resistance to immunotherapy

Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive and lethal cancer types. It is virtually resistant to any sort of therapy, including the most recent immunotherapies. These tumors are characterised by a strong hypoxic, nutrient poor, and acidic tumor microenvironment (TME), in which CD8+ T cells are excluded or absent. In the context of tumor acidity, the role of bicarbonate transporters, key regulators of pH homeostasis, has mostly been neglected so far. We recently identified SLC4A4 as the most abundant acid extruder in PDAC, expressed exclusively by ductal epithelial cell. Therefore, in this research proposal we aim to investigate whether and how SLC4A4 regulates the acidic TME and anti-tumor immunity in the context of PDAC. The success of this study might pave the way towards groundbreaking therapeutic strategies and combination regimens which are urgently required to tackle tumor resistance or refractoriness vis-à-vis immunotherapies.
Date:1 Oct 2021 →  Today
Keywords:Pancreatic cancer, Tumor acidity, Immunotherapy, Tumor microenvironment
Disciplines:Applied immunology , Cancer biology