Advancing Cancer Treatment Through Nanotechnology Driven Immunotherapy for Pancreatic Cancer

Pancreatic cancer is expected to be the most lethal cancer by 2030; among that, PDAC is the most prominent one, which is immune resistant, posing substantial hurdles to creating effective therapeutics. Despite the advancements in immunotherapy, its application in PDAC is less successful. Uniquely, PDAC tumors are "cold" to immune response mainly due to suppression of spatiotemporal immune signatures from cells and tumor microenvironment. Contrary to other immune-responsive tumors, immunotherapy in combination with chemotherapy in PDAC, is still diffusion-limiting to the drugs and less cytotoxic to cancer cells. Moreover, newer approaches exploring nanotechnology are being tried to make PDAC "hot" and immunogenic in nature and are promising. This review analyses the design strategies of nanosystems for effective spatiotemporal signaling to improve immune response to PDAC tumors. Particularly, that helps to overcome early evasion in phase I, and resistance to the antitumor immune response by modulating cellular and tumor microenvironment (TME) through the latest advancements in nanotechnology, immune mechanisms, and potential delivery routes for PDAC treatment. Ongoing and completed clinical trials of nanotechnology-driven immunotherapies in pancreatic cancer are also highlighted here. Overall, this approach of nanotechnological strategy to enhance immunotherapy in PDAC holds great promise and may contribute to a groundbreaking shift in the therapeutic management of PDAC and reduce the mortality rate of this lethal disease.