Crosstalk between the Tumor Microenvironment and Immune System in Pancreatic Ductal Adenocarcinoma: Potential Targets for New Therapeutic Approaches

Figure 2

Descriptive model representing pancreatic microenvironment changes during PDAC carcinogenesis. (a) In the normal pancreas, connective tissue, resident fibroblasts (PFs), pancreatic stellate cells (PSCs), immune cells, and vascular cells play a critical role in tissue repair and wound healing. (b) Pancreatic tissue damages and oncogenic mutations lead to carcinogenesis and disrupt normal communications between PSCs/PFs and immune and vascular cells, determining a favorable microenvironment for cancer progression. Soluble and growth factors produced by cancer cells activate PSCs and PFs that play a key role in the development and maintenance of stromal cancer compartment increasing extracellular matrix synthesis. (c) The intense fibrotic stromal reaction of PDAC is characterized by PSCs, PFs, vascular elements, immune cells, and acellular components such as collagens and hyaluronan, fibronectin, cytokines, and growth factors stored in the extracellular matrix. In this stage of disease MDSCs, M2, N2, and T_regs induce a protumor phenotype.