The Possible Role of Immunotherapy in Locally Advanced Pancreatic Cancer Treatment

Locally advanced pancreatic cancer (LAPC) represents a significant subset of pancreatic cancers and is characterized by a poor prognosis and limited treatment options. Conventional therapies, including chemoradiotherapy, have demonstrated limited success, prompting interest in innovative strategies, such as immunotherapy. This review evaluates the role of immunotherapy in LAPC.

For this review, a comprehensive search of the PubMed database was conducted in August 2024. After applying the exclusion criteria, 26 studies were included in the analysis.

Immune checkpoint inhibitors have produced inconsistent clinical outcomes, with modest improvements in progression-free survival and significant side effects. Cancer vaccines, particularly GVAX in combination regimens, have demonstrated potential, as have fibroblast activation protein (FAP) and mKRAS-specific amphiphile vaccines in preclinical and clinical settings. Chimeric antigen receptor (CAR) T-cell therapies targeting various antigens have yielded encouraging outcomes but have faced safety and efficacy challenges. Emerging approaches, including Toll-like receptor agonists, tumor-associated macrophage targeting, and radioimmunotherapy, have also shown preclinical promise but require further study. Despite numerous investigations, the overall impact of immunotherapy on LAPC remains limited. Some combination therapies involving checkpoint inhibitors, vaccines, and CAR T cells have shown positive outcomes; however, many are hindered by the immunosuppressive environment and toxicity of tumors. Recent studies emphasize the need for further research to refine these strategies and improve treatment options.

LAPC remains one of the deadliest malignancies, with immunotherapy offering potential but constrained by limited survival benefits and adverse effects. Further studies focusing on novel agents, refined combinations, and overcoming tumor resistance mechanisms are critical to improve outcomes for this challenging disease.