Figure 2.

Schematization of key molecular interactions in PDAC microenvironment. Pancreatic stellate cells (PSCs) and cancer-associated fibroblasts (CAFs) secrete immunosuppressive cytokines (IL-10, TGFβ), furthering their proliferation through positive feedback, polarizing tumor-associated neutrophiles (TANs) towards their pro-tumorigenic N2 phenotype and inhibiting cytotoxic T lymphocytes (CTLs) function. Additionally, the deposition of extracellular matrix (ECM) and the overproduction of adhesion molecules ligands (CXCL12, CXCL13) impede normal lymphocytes motility, promoting immune evasion. Abundancy of ECM, moreover, facilitates hypoxia, which activates the HIF-1α pathway. This, on one hand, induces autophagy in cancer-inhibiting cell populations, but, on the other hand, promotes neoangiogenesis and CTLs infiltration.