Role of targeted immunotherapy for pancreatic ductal adenocarcinoma (PDAC) treatment: An overview.

Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest solid tumors with a high mortality rate and poor survival rate. Depending on the tumor stage, PDAC is either treated by resection surgery, chemotherapies, or radiotherapies. Various chemotherapeutic agents have been used to treat PDAC, alone or in combination. Despite the combinations, chemotherapy exhibits many side-effects leading to an increase in the toxicity profile amongst the PDAC patients. Additionally, these standard chemotherapeutic agents have only a modest impact on patient survival due to their limited efficacy. PDAC was previously considered as an immunologically silent malignancy, but recent findings have demonstrated that effective immune-mediated tumor cell death can be used for its treatment. PDAC is characterized by an immunosuppressive tumor microenvironment accompanied by the major expression of myeloid-derived suppressor cells (MDSC) and M2 tumor-associated macrophages. In contrast, the expression of CD8+ T cells is significantly low. Additionally, infiltration of mast cells in PDAC correlates with the poor prognosis. Immunotherapeutic agents target the immunity mediators and empower them to suppress the tumor and effectively treat PDAC. Different targets are studied and exploited to induce an antitumor immune response in PDAC patients. In recent times, site-specific delivery of immunotherapeutics also gained attention among researchers to effectively treat PDAC. In the present review, existing immunotherapies for PDAC treatment along with their limitations are addressed in detail. The review also includes the pathophysiology, traditional strategies and significance of targeted immunotherapies to combat PDAC effectively. Separately, the identification of ideal targets for the targeted therapy of PDAC is also reviewed exhaustively. Additionally, the review also addresses the applications of targeted immunotherapeutics like checkpoint inhibitors, adoptive T-cell therapy etc.