Immunotherapy and Prevention of Pancreatic Cancer

Abstract

Pancreatic cancer is the third-leading cause of cancer mortality in the USA, recently surpassing breast cancer. A key component of pancreatic cancer's lethality is its acquired immune privilege, which is driven by an immunosuppressive microenvironment, poor T cell infiltration, and a low mutational burden. Although immunotherapies such as checkpoint blockade or engineered T cells have yet to demonstrate efficacy, a growing body of evidence suggests that orthogonal combinations of these and other strategies could unlock immunotherapy in pancreatic cancer. In this Review article, we discuss promising immunotherapies currently under investigation in pancreatic cancer and provide a roadmap for the development of prevention vaccines for this and other cancers.

Keywords: immunotherapy; pancreatic cancer; prevention vaccines.

Figure 1. Clinical status of immunotherapies in pancreatic cancer

Each line represents a single class of immunotherapy. The right end of each line indicates the latest stage of clinical trials that class of compounds has reached. Solid green arrows indicate ongoing trials. Red lines indicate negative trials. Dotted green arrow indicates successful trials in other malignancies.

Figure 2. Mechanisms of immunotherapies in PDA

Graphical representation of the immune response in pancreatic cancer indicating where each type of immunotherapy acts. See inset legend for significance of arrows. F = fibroblast, MDSC = myeloid derived suppressor cell, Mϕ = macrophage, DC = dendritic cell, CD8 = CD8 T cell, CD8_ex = exhausted CD8 T cell.