Overcoming the resistance of pancreatic cancer to immune checkpoint inhibitors

J Surg Oncol. 2017 Jul;116(1):55-62. doi: 10.1002/jso.24642. Epub 2017 Jun 19.

Abstract

Immunotherapy has become a new modality of cancer treatment, but has had a limited success in treating PDAC. A combination approach to immunotherapy, using both immune checkpoint inhibitors and immune activating agonists, is needed, as PDAC does not respond to single-agent checkpoint inhibitors. Studies have also supported using vaccine-based therapies to prime the tumor microenvironment of PDAC with effector T-cells. Other therapeutic strategies including epigenetic agents, stroma modulators, radiotherapy, and T-cell transfer therapies may also prime the tumor microenvironment to overcome resistance to immune checkpoint inhibitors.

Keywords: cancer vaccine; immune checkpoint inhibitor; immunotherapy; pancreatic cancer.

Publication types

  • Review

MeSH terms

  • Antibodies, Monoclonal / pharmacology
  • Antigens, CD / drug effects
  • Antigens, CD / immunology
  • Antigens, CD / metabolism
  • B7-H1 Antigen / drug effects
  • B7-H1 Antigen / immunology
  • B7-H1 Antigen / metabolism
  • CTLA-4 Antigen / drug effects
  • CTLA-4 Antigen / immunology
  • CTLA-4 Antigen / metabolism
  • Cancer Vaccines
  • Cytokines / pharmacology
  • Humans
  • Immunotherapy*
  • Ipilimumab
  • Lymphocyte Activation Gene 3 Protein
  • Macrophages / metabolism
  • Myeloid-Derived Suppressor Cells / metabolism
  • Pancreatic Neoplasms / immunology*
  • Pancreatic Neoplasms / metabolism
  • Pancreatic Neoplasms / therapy*
  • T-Lymphocytes, Regulatory / metabolism
  • Tumor Microenvironment

Substances

  • Antibodies, Monoclonal
  • Antigens, CD
  • B7-H1 Antigen
  • CD274 protein, human
  • CTLA-4 Antigen
  • Cancer Vaccines
  • Cytokines
  • Ipilimumab
  • Lymphocyte Activation Gene 3 Protein
  • Lag3 protein, human