Myeloid Cell Mediated Immune Suppression in Pancreatic Cancer

Cell Mol Gastroenterol Hepatol. 2021;12(5):1531-1542. doi: 10.1016/j.jcmgh.2021.07.006. Epub 2021 Jul 22.

Abstract

Pancreatic ductal adenocarcinoma (PDA), the most common pancreatic cancer, is a nearly universally lethal malignancy. PDA is characterized by extensive infiltration of immunosuppressive myeloid cells, including tumor-associated macrophages and myeloid-derived suppressor cells. Myeloid cells in the tumor microenvironment inhibit cytotoxic T-cell responses promoting carcinogenesis. Immune checkpoint therapy has not been effective in PDA, most likely because of this robust immune suppression, making it critical to elucidate mechanisms behind this phenomenon. Here, we review myeloid cell infiltration and cellular crosstalk in PDA progression and highlight current therapeutic approaches to target myeloid cell-driven immune suppression.

Publication types

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

MeSH terms

  • Animals
  • Biomarkers
  • Cell Communication
  • Cell Lineage / immunology
  • Cell Transformation, Neoplastic / genetics
  • Cell Transformation, Neoplastic / immunology
  • Cell Transformation, Neoplastic / metabolism
  • Disease Management
  • Disease Susceptibility
  • Drug Resistance, Neoplasm
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Immunomodulation*
  • Myeloid Cells / immunology*
  • Myeloid Cells / metabolism*
  • Myeloid-Derived Suppressor Cells / immunology
  • Myeloid-Derived Suppressor Cells / metabolism
  • Myeloid-Derived Suppressor Cells / pathology
  • Neoplasm Metastasis
  • Pancreatic Neoplasms / etiology*
  • Pancreatic Neoplasms / metabolism*
  • Pancreatic Neoplasms / pathology
  • Pancreatic Neoplasms / therapy
  • Signal Transduction
  • Single-Cell Analysis / methods
  • Tumor Microenvironment / immunology*
  • Tumor-Associated Macrophages / immunology
  • Tumor-Associated Macrophages / metabolism
  • Tumor-Associated Macrophages / pathology

Substances

  • Biomarkers