Targeting IRAK4 signaling in PDAC: Turning the ‘cold’ tumors to ‘hot’ ones.

Immunotherapy has revolutionized the cancer chemotherapy paradigm for recalcitrant tumors, such as metastatic melanomas and non–small cell lung cancers. However, current immunotherapeutic strategies have shown little success against pancreatic ductal adenocarcinomas (PDACs). This lack of success against PDACs can be attributed to a limited presence of immune cells and their activity in the immune-suppressive tumor microenvironment (TME), thereby making it an “immunologically cold” tumor.1 The PDAC stroma facilitates complex interactions among suppressive cancer-associated fibroblasts, myeloid cells, lymphocytes, and various chemokines, which altogether creates a hostile environment for adaptive immune responses, thereby causing poor infiltration and exhausted phenotypes of effector T cells within the pancreatic tumors.