Article Text

PDF
Overcoming immune evasion in pancreatic cancer: the combination matters
  1. Patrick Michl,
  2. Sebastian Krug
  1. Department of Internal Medicine I, Martin-Luther-University Halle-Wittenberg, Halle, Germany
  1. Correspondence to Professor Patrick Michl, Department of Internal Medicine I, Martin-Luther-University Halle-Wittenberg, Halle 06120, Germany; patrick.michl{at}uk-halle.de

Statistics from Altmetric.com

Pancreatic ductal adenocarcinoma (PDAC) is projected to surpass breast, prostate and colorectal cancers to become the second leading cause of cancer-related death by 2030.1 Despite recent advances in combination chemotherapies, the prognosis remains appallingly poor. Immunotherapeutic approaches using checkpoint inhibitors that have been established as novel pillar of cancer therapy for several other tumour entities have largely failed to improve survival in pancreatic cancer when used as single agents.2 Increasing preclinical and clinical evidence suggests that the immunosuppressive tumour microenvironment (TME) in pancreatic cancer, comprising up to 90% of the tumour volume, functions as an important mediator of therapy resistance and might be responsible for the failure of immunotherapy. Several molecular mechanisms have been identified which enhance the immunosuppressive micromilieu, among them upregulation of inhibitory signalling molecules such as PDL1, CTLA4 and LAG3 or key metabolic enzymes suppressing the antitumorous immune cell function. In addition, tumour-infiltrating bone marrow-derived myeloid cells including tumour-associated macrophages (TAM) and neutrophils (TAN) have been recognised as important mediators of immune evasion.3 These myeloid cells are recruited from the bone marrow to the site of the tumour by distinct chemokine pathways co-opted by the tumour cells to facilitate myeloid cell attraction. In particular, the role of TAN has recently attracted increasing interest …

View Full Text

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.