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

Figure 3

Crosstalk between cancer cells, the TME, the immune system, and potential therapeutic targets. TME components interplay with cancer cells (black arrows) through cytokines and growth factors becoming active and causing tumor proliferation, invasiveness, and metastasization. Communication between PDAC cells and activated PSCs/PFs induces soluble factor secretion increasing ECM production. This continued crosstalk determines immunosuppressive effects on TME immune infiltrate (red lines). Tumor-infiltrating lymphocytes produce high levels of PD-1 and interact with PDL-1 overexpressed by PDAC cells, resulting in T lymphocyte depletion. Several molecules (target agents or immunotherapies) with different mechanisms of action (green boxes) may interfere in the crosstalk between cancer cells and the TME restoring immune response, directly killing tumor cells, or destroying ECM components (green lines).