Antitumor activity with or without anti-CTLA4 monoclonal antibody (mAb) therapy has been observed in patients with melanoma, and major tumor regressions have been observed in patients with pancreatic cancer, mesothelioma, and other tumors in combination with chemotherapy.
Despite the fact that immunotherapy with checkpoint blockade (e.g., anti-cytotoxic T-lymphocyte antigen 4 [CTLA-4] and anti-programmed cell death 1 [PD-1]/PD-L1 antibodies) has shown remarkable and durable responses in various cancer types, the application of checkpoint inhibitors in pancreatic cancer has been disappointing so far.
Emerging evidence suggests that the gut microbiota may influence not only the efficacy of cancer chemotherapies and novel targeted immunotherapies such as anti-CTLA4 and anti-CD274 therapies but also the occurrence of postoperative complications after hepatobiliary and pancreatic surgery, which have been associated with tumor recurrence and worse patient survival in hepatobiliary-pancreatic cancers.
These results suggest that CTLA-4 49G>A polymorphism is involved in susceptibility to developing pancreatic cancer, alone and in a gene-environment interaction manner.