Targeting Cancer Stem Cells and Their Niche: Current Therapeutic Implications and Challenges in Pancreatic Cancer

Figure 2

The potential role of pancreatic CSCs in cancer immunoediting. Elimination (left): in the elimination process, most of pancreatic cancer cells can be successfully detected and destroyed by the innate and adaptive system. However, pancreatic CSCs are believed to be immunologically privileged like normal stem cells. Low immunogenicity prevents pancreatic CSCs from recognition and elimination by the host immune system. Equilibrium (middle): in the equilibrium process, the immune system and pancreatic cancer cells that have survived the elimination process enter into a dynamic equilibrium. The function of the immune system can be negatively regulated by cancer cells and stromal cells. The majority of pancreatic cancer cells are destroyed, but some cancer cells acquire the ability to avoid immune destruction. The equilibrium process is functionally similar to the state of tumor dormancy. Escape (right): in the escape process, pancreatic cancer cells can inhibit host anticancer immunity by secretion of immunosuppressive factors and by recruitment of stromal cells, such as Tregs and MDSCs. Besides, PSCs, CAFs, and TAMs also support pancreatic CSC growth and promote immunosuppression. The immunosuppressive niche allows pancreatic CSCs to rapidly produce specialized cancer cells with high metastatic potential or chemoresistance. Finally, pancreatic CSCs and their differentiated progeny progressively grow into a visible tumor in the pancreas and even metastasize to distant sites.