Immunotherapy and Pancreatic Cancer: A Lost Challenge?

Abstract

Although immunotherapy has proved to be a very efficient therapeutic strategy for many types of tumors, the results for pancreatic cancer (PC) have been very poor. Indeed, chemotherapy remains the standard treatment for this tumor in the advanced stage. Clinical data showed that only a small portion of PC patients with high microsatellite instability/mismatch repair deficiency benefit from immunotherapy. However, the low prevalence of these alterations was not sufficient to lead to a practice change in the treatment strategy of this tumor. The main reasons for the poor efficacy of immunotherapy probably lie in the peculiar features of the pancreatic tumor microenvironment in comparison with other malignancies. In addition, the biomarkers usually evaluated to define immunotherapy efficacy in other cancers appear to be useless in PC. This review aims to describe the main features of the pancreatic tumor microenvironment from an immunological point of view and to summarize the current data on immunotherapy efficacy and immune biomarkers in PC.

Keywords: PD-1; PD-L1; TMB; immune biomarkers; immunotherapy; microsatellite instability; mismatch repair deficiency; pancreatic cancer; tumor microenvironment.

Figure 1

Illustration of the various possible interactions among immune cells in the pancreatic tumor microenvironment. CAFs: cancer-associated fibroblasts; GM-CSF: granulocyte-macrophage colony-stimulating factor; MDSC: myeloid-derived suppressor cells; NK: natural killer; PD-1: programmed death-1; PD-L1: programmed death-ligand 1; TAMs: tumor-associated macrophages; TANs: tumor-associated neutrophils.