Immunotherapy in pancreatic ductal adenocarcinoma: an emerging entity?

Abstract

The genomic-plasticity of the immune system creates a broad immune repertoire engaged to tackle cancer cells. Promising clinical activity has been observed with several immune therapy strategies in solid tumors including melanoma, lung, kidney, and bladder cancers, albeit as yet immunotherapy-based treatment approaches in pancreatic ductal adenocarcinoma (PDAC) remain to have proven value. While translational and early clinical studies have demonstrated activation of antitumor immunity, most recent late-phase clinical trials have not confirmed the early promise in PDAC except in MSI-High PDAC patients. These results may in part be explained by multiple factors, including the poorly immunogenic nature of PDAC along with immune privilege, the complex tumor microenvironment, and the genetic plasticity of PDAC cells. These challenges have led to disappointments in the field, nonetheless they have also advanced our understanding that may tailor the future steps for immunotherapy for PDAC. Therefore, there is significant hope that progress is on the horizon.

Keywords: PD-1; PD-L1; immune evasion; immunotherapy; mismatch repair; pancreatic cancer.

Figure 1.

Interaction between immune and cancer cells and their receptors (PD-1, PD-L1, and CTLA4), which are targeted by monoclonal antibodies.