Modulation of PD-1/PD-L1 axis in myeloid-derived suppressor cells by anti-cancer treatments

Cell Immunol. 2021 Apr:362:104301. doi: 10.1016/j.cellimm.2021.104301. Epub 2021 Feb 4.

Abstract

Immuno checkpoint blockade (ICB) targeting the PD-1/PD-L1 axis is the main breakthrough for the treatment of several cancers. Nevertheless, not all patients benefit from this treatment and clinical response not always correlates with PD-L1 expression by tumor cells. The tumor microenvironment, including myeloid derived suppressor cells (MDSCs), can influence therapeutic resistance to ICB. MDSCs also express PD-L1, which contributes to their suppressive activity. Moreover, anticancer therapies including chemotherapy, radiotherapy, hormone- and targeted- therapies can modulate MDSCs recruitment, activity and PD-L1 expression. Such effects can be induced also by innovative anticancer treatments targeting metabolism and lifestyle. The outcome on cancer progression can be either positive or negative, depending on tumor type, treatment schedule and possible combination with ICB. Further studies are needed to better understand the effects of cancer therapies on the PD-1/PD-L1 axis, to identify patients that could benefit from combinatorial regimens including ICB or that rather should avoid it.

Keywords: Cancer; Immunotherapy; MDSC; PD-1/PD-L1.

Publication types

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

MeSH terms

  • B7-H1 Antigen / immunology
  • B7-H1 Antigen / metabolism*
  • B7-H1 Antigen / physiology
  • Cell Line, Tumor
  • Humans
  • Immunotherapy
  • Myeloid-Derived Suppressor Cells / immunology*
  • Myeloid-Derived Suppressor Cells / metabolism
  • Myeloid-Derived Suppressor Cells / physiology
  • Neoplasms / immunology
  • Neoplasms / therapy
  • Programmed Cell Death 1 Receptor / immunology
  • Programmed Cell Death 1 Receptor / metabolism*
  • Tumor Microenvironment

Substances

  • B7-H1 Antigen
  • CD274 protein, human
  • PDCD1 protein, human
  • Programmed Cell Death 1 Receptor