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Pancreatic Cancer and Immunotherapy: Resistance Mechanisms and Proposed Solutions

  • Elaine TanEmail author
  • Bassel El-Rayes
Review Article

Abstract

Background

Pancreatic ductal adenocarcinoma (PDAC) continues to be one of the most aggressive and lethal diseases in the world. The success of immunotherapy in other types of malignancy has led to further trials to understand better the role of immunotherapy in PDAC. However, initial studies with immunotherapy, namely, the checkpoint inhibitors, in PDAC have not been met with the same outcomes. The purpose of this review is to identify and discuss the various resistance mechanisms of PDAC to immunotherapy (pancreatic stroma, genetic predisposition/epigenetics, and the immune inhibitory cells, cytokines, soluble factors, and enzymes that comprise the tumor microenvironment) and the solutions currently being studied to overcome them.

Conclusions

Various preclinical and early clinical studies have shown that immunotherapy, especially checkpoint inhibitors, in PDAC may be efficacious as part of a multi-modal treatment, in combination with other therapies that target these resistance mechanisms. Several clinical trials are ongoing to explore this concept further.

Keywords

Pancreatic ductal adenocarcinoma Immunotherapy Resistance 

Notes

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.

Informed Consent

For this type of study, formal consent is not required.

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Internal MedicineEmory University School of MedicineAtlantaUSA
  2. 2.Department of Hematology and Medical OncologyEmory UniversityAtlantaUSA
  3. 3.Winship Cancer InstituteEmory UniversityAtlantaUSA

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