Immunotherapy for pancreatic cancer: Barriers and breakthroughs

Abstract

Immunotherapy is a rapidly growing field and represents a paradigm shift in the treatment of malignancies as it offers a new therapeutic approach beyond surgery, conventional chemotherapy, and radiation treatment. Targeting immune checkpoints, such as cytotoxic T-lymphocyte-associated antigen 4 and programmed death 1/programmed death ligand 1 has had immense clinical success resulting in sustained treatment response for a subset of patients with certain malignancies such as melanoma, non-small-cell lung cancer, urothelial carcinoma, squamous cell carcinoma of the head and neck, renal cell cancer, hepatocellular cancer, and metastatic colorectal cancer. Importantly, there has been limited success in the use of immunotherapy in the treatment of pancreatic cancer. Investigation into the complex tumor microenvironment of pancreatic cancer that is composed of immune cells, stromal cells, and extracellular matrix proteins has begun to shed light on important attributes of this microenvironment that act as barriers to the effective use of immunotherapy. In this review, we will discuss the progress that has been made in treating pancreatic cancer with immunotherapy, the barriers that have limited treatment success, and breakthroughs with combination treatments that hold promise for the future.

Keywords: cancer vaccine; immune checkpoint; immunotherapy; pancreatic cancer; tumor microenvironment.

Figure 1

Abundant desmoplastic stroma of pancreatic cancer. A, Hematoxylin and eosin‐stained primary pancreatic ductal adenocarcinoma (10×), showing abundant desmoplastic stroma surrounding tumor epithelial cells. B, Interaction of tumor epithelial cells and stromal components can impede drug delivery, enhance or impair tumor growth and metastasis, and alter immune surveillance of tumors