Challenges and Opportunities for Pancreatic Cancer Immunotherapy

Cancer Cell. 2020 Dec 14;38(6):788-802. doi: 10.1016/j.ccell.2020.08.004. Epub 2020 Sep 17.

Abstract

Pancreatic ductal adenocarcinoma (PDA) is among the most immune-resistant tumor types. Its unique genomic landscape shaped by oncogenic drivers promotes immune suppression from the earliest stages of tumor inception to subvert adaptive T cell immunity. Single-agent immune modulators have thus far proven clinically ineffective, and multi-modal therapies targeting mechanisms of immunotherapy resistance are likely needed. Here, we review novel immunotherapy strategies currently under investigation to (1) confer antigen specificity, (2) enhance T cell effector function, and (3) neutralize immunosuppressive elements within the tumor microenvironment that may be rationally combined to untangle the web of immune resistance in PDA and other tumors.

Keywords: immunotherapy; pancreatic cancer.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Carcinoma, Pancreatic Ductal / drug therapy*
  • Carcinoma, Pancreatic Ductal / immunology
  • Clinical Trials as Topic
  • Drug Resistance, Neoplasm
  • Humans
  • Immunotherapy / methods*
  • Pancreatic Neoplasms / immunology
  • Pancreatic Neoplasms / therapy*
  • Tumor Escape
  • Tumor Microenvironment