Genomics meets immunity in pancreatic cancer: Current research and future directions for pancreatic adenocarcinoma immunotherapy

  • Jacob S. Bowers Department of Surgery, Medical University of South Carolina; Hollings Cancer Center, Medical University of South Carolina; Department of Microbiology and Immunology, Medical University of South Carolina, United States.
  • Stefanie R. Bailey Cellular Immunotherapy Program, Massachusetts General Hospital; Harvard Medical School, United States.
  • Mark P. Rubinstein Department of Surgery, Medical University of South Carolina; Hollings Cancer Center, Medical University of South Carolina; Department of Microbiology and Immunology, Medical University of South Carolina, United States.
  • Chrystal M. Paulos Hollings Cancer Center, Medical University of South Carolina; Department of Microbiology and Immunology, Medical University of South Carolina; Department of Dermatology and Dermatologic Surgery, Medical University of South Carolina, United States.
  • E. Ramsay Camp | campe@musc.edu Department of Surgery, Medical University of South Carolina; Hollings Cancer Center, Medical University of South Carolina; Ralph H. Johnson VA Medical Center, South Carolina, United States.

Abstract

Pancreatic adenocarcinoma (PDAC) remains a formidable disease that needs improved therapeutic strategies. Even though immunotherapy has revolutionized treatment for various solid tumor types, it remains largely ineffective in treating individuals with PDAC. This review describes how the application of genome-wide analysis is revitalizing the field of PDAC immunotherapy. Major themes include new insights into the body’s immune response to the cancer, and key immunosuppressive elements that blunt that antitumor immunity. In particular, new evidence indicates that T cell-based antitumor immunity against PDAC is more common, and more easily generated, than previously thought. However, equally common are an array of cellular and molecular defenses employed by the tumor against those T cells. These discoveries have changed how current immunotherapies are deployed and have directed development of novel strategies to better treat this disease. Thus, the impact of genomic analysis has been two-fold: both in demonstrating the heterogeneity of immune targets and defenses in this disease, as well as providing a powerful tool for designing and identifying personalized therapies that exploit each tumor’s unique phenotype. Such personalized treatment combinations may be the key to developing successful immunotherapies for pancreatic adenocarcinoma.

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Published
2019-08-01
Section
Reviews
Keywords:
Pancreatic adenocarcinoma, immunology, genomics, immunotherapy, neoantigen, T cell, CAR T cell, desmoplastic, vaccine, immunosuppression.
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How to Cite
Bowers, J., Bailey, S. R., Rubinstein, M. P., Paulos, C. M., & Camp, E. R. (2019). Genomics meets immunity in pancreatic cancer: Current research and future directions for pancreatic adenocarcinoma immunotherapy. Oncology Reviews, 13(2). https://doi.org/10.4081/oncol.2019.430