A Complex Metabolic Network Confers Immunosuppressive Functions to Myeloid-Derived Suppressor Cells (MDSCs) within the Tumour Microenvironment

Cells. 2021 Oct 9;10(10):2700. doi: 10.3390/cells10102700.

Abstract

Myeloid-derived suppressor cells (MDSCs) constitute a plastic and heterogeneous cell population among immune cells within the tumour microenvironment (TME) that support cancer progression and resistance to therapy. During tumour progression, cancer cells modify their metabolism to sustain an increased energy demand to cope with uncontrolled cell proliferation and differentiation. This metabolic reprogramming of cancer establishes competition for nutrients between tumour cells and leukocytes and most importantly, among tumour-infiltrating immune cells. Thus, MDSCs that have emerged as one of the most decisive immune regulators of TME exhibit an increase in glycolysis and fatty acid metabolism and also an upregulation of enzymes that catabolise essential metabolites. This complex metabolic network is not only crucial for MDSC survival and accumulation in the TME but also for enhancing immunosuppressive functions toward immune effectors. In this review, we discuss recent progress in the field of MDSC-associated metabolic pathways that could facilitate therapeutic targeting of these cells during cancer progression.

Keywords: cancer; immunometabolism; inflammation; myeloid-derived suppressor cells (MDSC); tumour-microenvironment (TME).

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Humans
  • Immunosuppression Therapy*
  • Metabolic Networks and Pathways*
  • Molecular Targeted Therapy
  • Myeloid-Derived Suppressor Cells / immunology*
  • Myeloid-Derived Suppressor Cells / metabolism*
  • Neoplasms / immunology
  • Neoplasms / pathology
  • Neoplasms / therapy
  • Tumor Microenvironment / immunology*