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Pancreatic Cancer and Immunotherapy: Resistance Mechanisms and Proposed Solutions

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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.

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Authors and Affiliations

  1. Department of Internal Medicine, Emory University School of Medicine, 100 Woodruff Circle Suite, 327, Atlanta, GA, 30322, USA

    Elaine Tan

  2. Department of Hematology and Medical Oncology, Emory University, Atlanta, GA, USA

    Bassel El-Rayes

  3. Winship Cancer Institute, Emory University, 1365 Clifton Road, Atlanta, GA, 30322, USA

    Bassel El-Rayes

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  1. Elaine Tan
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  2. Bassel El-Rayes
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Correspondence to Elaine Tan.

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Tan, E., El-Rayes, B. Pancreatic Cancer and Immunotherapy: Resistance Mechanisms and Proposed Solutions. J Gastrointest Canc 50, 1–8 (2019). https://doi.org/10.1007/s12029-018-0179-z

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  • DOI: https://doi.org/10.1007/s12029-018-0179-z

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