Cellular determinants and therapeutic implications of inflammation in pancreatic cancer

Pharmacol Ther. 2019 Sep;201:202-213. doi: 10.1016/j.pharmthera.2019.05.012. Epub 2019 May 31.

Abstract

Inflammation is a hallmark of cancer. For pancreatic ductal adenocarcinoma (PDAC), malignant cells arise in the context of a brisk inflammatory cell infiltrate surrounded by dense fibrosis that is seen beginning at the earliest stages of cancer conception. This inflammatory and fibrotic milieu supports cancer cell escape from immune elimination and promotes malignant progression and metastatic spread to distant organs. Targeting this inflammatory reaction in PDAC by inhibiting or depleting pro-tumor elements and by engaging the potential of inflammatory cells to acquire anti-tumor activity has garnered strong research and clinical interest. Herein, we describe the current understanding of key determinants of inflammation in PDAC; mechanisms by which inflammation drives immune suppression; the impact of inflammation on metastasis, therapeutic resistance, and clinical outcomes; and strategies to intervene on inflammation for providing therapeutic benefit.

Keywords: Cancer; Clinical trials; Immune evasion; Immunosurveillance; Immunotherapy; Inflammation; Macrophages; Metastasis; Neutrophils; Pancreatic ductal adenocarcinoma; T cells; Therapeutic resistance; Treatment paradigms; Tumor microenvironment; Vaccines.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Carcinoma, Pancreatic Ductal / immunology
  • Carcinoma, Pancreatic Ductal / pathology*
  • Carcinoma, Pancreatic Ductal / therapy
  • Humans
  • Immunotherapy / methods
  • Inflammation / immunology
  • Inflammation / pathology*
  • Inflammation / therapy
  • Neoplasm Metastasis
  • Pancreatic Neoplasms / immunology
  • Pancreatic Neoplasms / pathology*
  • Pancreatic Neoplasms / therapy