Overcoming immune evasion in pancreatic cancer: the combination matters

Pancreatic ductal adenocarcinoma (PDAC) is projected to surpass breast, prostate and colorectal cancers to become the second leading cause of cancer-related death by 2030.1 Despite recent advances in combination chemotherapies, the prognosis remains appallingly poor. Immunotherapeutic approaches using checkpoint inhibitors that have been established as novel pillar of cancer therapy for several other tumour entities have largely failed to improve survival in pancreatic cancer when used as single agents.2 Increasing preclinical and clinical evidence suggests that the immunosuppressive tumour microenvironment (TME) in pancreatic cancer, comprising up to 90% of the tumour volume, functions as an important mediator of therapy resistance and might be responsible for the failure of immunotherapy. Several molecular mechanisms have been identified which enhance the immunosuppressive micromilieu, among them upregulation of inhibitory signalling molecules such as PDL1, CTLA4 and LAG3 or key metabolic enzymes suppressing the antitumorous immune cell function. In addition, tumour-infiltrating bone...

https://ift.tt/2jECiJS