Current Status of Immunotherapy for Pancreatic Cancer

Abstract

Pancreatic ductal adenocarcinoma remains an awfully fatal malignancy whose five-year survival rate was merely 11%. Its immunosuppressive tumor microenvironment, characterized by immune cell dysfunction, limits the efficacy of conventional therapies. Immunotherapy has become the fifth major strategy of cancer therapy after chemotherapy, surgery, targeted therapy and radiotherapy, showing revolutionary therapeutic effects in a variety of solid tumors. Understanding the immune-related mechanisms of pancreatic cancer and developing targeted immunotherapy strategies have become the top priorities of current research. Recent advances show promise through strategies such as engineered chimeric antigen receptor-modified T(CAR-T) cells secreting cytokines like Chemokine (C-C motif) ligand 19(CCL19) and interleukin-7(IL-7), which enhance T-cell persistence and tumor clearance. Immune checkpoint blockade (ICB), though ineffective alone, benefits from combinations with metabolic modulators, β-blockers, or microbiome metabolites like trimethylamine N-oxide(TMAO). Oncolytic virotherapy combined with chemotherapy or immunomodulators can degrade stroma and stimulate antitumor immunity. Despite progress, challenges remain due to TME immunosuppression and low immunogenicity for pure immunotherapy. Future efforts should focus on combination therapies and microenvironment reprogramming to improve outcomes.