Role of the immune system in pancreatic cancer progression and immune modulating treatment strategies

Kostas Sideras, Henri Braat, Jaap Kwekkeboom, Casper van Eijck, Maikel Peppelenbosch, Stefan Sleijfer, Marco Bruno

Research output: Contribution to journalArticleAcademicpeer-review

147 Citations (Scopus)

Abstract

Traditional chemotherapeutics have largely failed to date to produce significant improvements in pancreatic cancer survival. One of the reasons for the resilience of pancreatic cancer towards intensive treatment is that the cancer is capable of high jacking the immune system: during disease progression the immune system is converted from a system that attacks tumor cells into a support structure for the cancer, exerting trophic actions on the cancer cells. This turn-around of immune system action is achieved through mobilization and activation of regulatory T cells, myeloid derived suppressor cells, tumor-associated macrophages and fibroblasts, all of which suppress CD8 T cells and NK cells. This immune suppression occurs both through the expression of tolerance-inducing cell surface molecules, such as PD-L1, as well as through the production of "tolerogenic" cytokines, such as IL-10 and TGF-beta. Based on the accumulating insight into the importance of the immune system for the outcome of pancreatic cancer patients multiple new immunotherapeutic approaches against pancreatic cancer are being currently tested in clinical trials. In this review we give an overview of both the immune escaping mechanisms of pancreatic cancer as well as the new immune related therapeutic strategies currently being tested in pancreatic cancer clinical trials. (C) 2013 Elsevier Ltd. All rights reserved.
Original languageUndefined/Unknown
Pages (from-to)513-522
Number of pages10
JournalCancer Treatment Reviews
Volume40
Issue number4
DOIs
Publication statusPublished - 2014

Research programs

  • EMC MM-03-86-01
  • EMC MM-03-86-08
  • EMC MM-04-20-01

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