Expression of checkpoint molecules on myeloid-derived suppressor cells

Marlene Ballbach, Angelika Dannert, Anurag Singh, Darina M. Siegmund, Rupert Handgretinger, Luca Piali, Nikolaus Rieber, Dominik Hartl

Research output: Contribution to journalArticlepeer-review

78 Scopus citations

Abstract

Myeloid-derived suppressor cells (MDSCs) are a heterogeneous cell population expanded in cancer, infection and autoimmunity capable of suppressing T-cell functions. Checkpoint inhibitors have emerged as a key therapeutic strategy in immune-oncology. While checkpoint molecules were initially associated with T cell functions, recent evidence suggests a broader expression and function in innate myeloid cells. Previous studies provided first evidence for a potential role for checkpoints on MDSCs, yet the human relevance remained poorly understood. Therefore, we investigated the expression and functional relevance of checkpoint molecules in human MDSC-T-cell interactions. Our studies demonstrate that programmed death-ligand 1 (PD-L1) is expressed on granulocytic MDSCs upon co-culture with T cells. Transwell experiments showed that cell-to-cell contact was required for MDSC-T-cell interactions and antibody blocking studies showed that targeting PD-L1 partially impaired MDSC-mediated T-cell suppression. Collectively, these studies suggest a role for PD-L1 in human MDSC function and thereby expand the functionality of this checkpoint beyond T cells, which could pave the way for further understanding and therapeutic targeting of PD-1/PD-L1 in innate immune-mediated diseases.

Original languageEnglish
Pages (from-to)1-6
Number of pages6
JournalImmunology Letters
Volume192
DOIs
StatePublished - Dec 2017
Externally publishedYes

Keywords

  • Checkpoints
  • MDSC
  • Myeloid-derived suppressor cells
  • PD-1
  • PD-L1
  • T-cell suppression

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