Enriched cancer stem cells, dense stroma, and cold immunity: Interrelated events in pancreatic cancer

Cold tumors generally show low mutational burden and low infiltration of effector T cells. The pancreas, prostate, ovary, breast, and colon are placed into the category of cold tumors. In such tumors, effector T cells are either excluded from the tumor area or taken away from being in contact with tumor cells. The stromal reaction in the form of desmoplasia is important for the pathogenesis of tumors like the pancreas. Besides acting as a barrier for the penetration of drugs into the tumor area, the dense stroma presumably creates an immunosuppressive tumor microenvironment (TME), which accounts for low responses from tumor to immunotherapy. Cancer stem cells (CSCs) are an important part of the immunosuppressive complex within the TME. The presence of CSCs within the TME is related negatively to the activity of the antitumor immune system. Here, the question is how desmoplastic aggregates can influence the functionality of CSCs for promoting a cold pancreatic tumor immunity? This review is aimed at responding to this question, the disruption of which can be an effective strategy for improving responses from cold tumors to immunotherapy.