title: Role of the immune system in pancreatic cancer progression and immune modulating treatment strategies.
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-β. 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.
authors: Erasmus University Medical Center, Department of Gastroenterology and Hepatology, NA-0621's, Gravendijkwal 230, 3015 CE Rotterdam, The Netherlands. Electronic address: k.sideras@erasmusmc.nl.
authors: K
authors: K
authors: Sideras
authors: Erasmus University Medical Center, Department of Gastroenterology and Hepatology, Hs-510's, Gravendijkwal 230, 3015 CE Rotterdam, The Netherlands. Electronic address: h.braat@erasmusmc.nl.
authors: H
authors: H
authors: Braat
authors: Erasmus University Medical Center, Laboratory of Gastroenterology and Hepatology, NA-1009's, Gravendijkwal 230, 3015 CE Rotterdam, The Netherlands. Electronic address: j.kwekkeboom@erasmusmc.nl.
authors: J
authors: J
authors: Kwekkeboom
authors: Erasmus University Medical Center, Department of Surgery, Room H-818k's Gravendijkwal 230, 3015 CE Rotterdam, The Netherlands. Electronic address: c.vaneijck@erasmusmc.nl.
authors: C H
authors: CH
authors: van Eijck
authors: Erasmus University Medical Center, Laboratory of Gastroenterology and Hepatology, Na-1007's, Gravendijkwal 230, 3015 CE Rotterdam, The Netherlands. Electronic address: m.peppelenbosch@erasmusmc.nl.
authors: M P
authors: MP
authors: Peppelenbosch
authors: Erasmus University Medical Center, Department of Oncology, He-116's Gravendijkwal 230, 3015 CE Rotterdam, The Netherlands. Electronic address: s.sleijfer@erasmusmc.nl.
authors: S
authors: S
authors: Sleijfer
authors: Erasmus University Medical Center, Department of Gastroenterology and Hepatology, H-358's, Gravendijkwal 230, 3015 CE Rotterdam, The Netherlands. Electronic address: m.bruno@erasmusmc.nl.
authors: M
authors: M
authors: Bruno
mesh_terms: D000818:Animals; D016207:Cytokines / Q000276:immunology; D018450:Disease Progression; D006801:Humans; D007111:Immunity, Cellular / Q000276:immunology; D007167:Immunotherapy / Q000379:methods*; D010190:Pancreatic Neoplasms / Q000276:immunology* / Q000473:pathology / Q000628:therapy*
chemical_list: D016207:Cytokines
keywords: Fibroblasts; Immune inhibitory ligands; Immune system; Immunotherapy; Pancreatic cancer; Review; T regulatory cells; Th1; Th2; Vaccination