Extra-cellular matrix, angiogenesis and the immunotherapy of pancreatic ductal adenocarcinoma

Pancreatic ductal adenocarcinoma [PDAC] continues to be associated with a dismal prognosis with 5-year survival rates consistently less than 5% [1]. One of the main histopathological features of PDAC is the abnormal deposition of stromal fibrosis, also known as desmoplasia. It constitutes the tumor microenvironment in which various sub-populations of the innate and adaptive immune system are distributed. This extensive stromal desmoplasia has been suggested to favor tumor development and most importantly to prevent the diffusion of chemotherapeutic agents. Preclinical models have also shown that targeting the signaling pathways leading to extra-cellular matrix [ECM] protein synthesis could increase drug diffusion in the neoplastic tissue. However, PDAC clinical trials have yet to show a significant benefit from these therapeutic strategies [2].