4.7 Article

Trials and tribulations of pancreatic cancer immunotherapy

Journal

CANCER LETTERS
Volume 504, Issue -, Pages 1-14

Publisher

ELSEVIER IRELAND LTD
DOI: 10.1016/j.canlet.2021.01.031

Keywords

Pancreatic cancer; Immunotherapy; Immune checkpoint inhibition; Tumor microenvironment; Tumor immunology

Categories

Funding

  1. Veterans Affairs Merit Award [I01BX002703, I01BX002922]
  2. Veterans Affairs Career Scientist Award [IK6 BX004855]
  3. NIH [CA07059, F30CA236031, R01CA217907, R21CA255291]
  4. UIC Award for Graduate Research

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Immunotherapy has revolutionized cancer treatment in the past decade, but has faced exceptional challenges in pancreatic ductal adenocarcinoma. Despite many different immunotherapies being explored in clinical trials, few have shown significant therapeutic efficacy.
Immunotherapy has revolutionized cancer treatment in the last decade, and strategies to re-activate cytotoxic immunity are now standard of care in several malignancies. Despite rapid advances in immunotherapy for most solid cancers, progress in immunotherapy against pancreatic ductal adenocarcinoma (PDAC) has been exceptionally difficult. This is true for several approaches, most notably immune checkpoint inhibitors (ICIs) and GM-CSF cell-based vaccines (GVAX). Though many immunotherapies have been explored in clinical trials, few have shown significant therapeutic efficacy. Further, many have shown high rates of serious adverse effects and dose-limiting toxicities, and to date, immunotherapy regimens have not been successfully implemented in PDAC. Here, we provide a comprehensive summary of the key clinical trials exploring immunotherapy in PDAC, followed by a brief discussion of emerging molecular mechanisms that may explain the relative failure of immunotherapy in pancreas cancer thus far.

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