Monocytic myeloid-derived suppressor cells home to tumor-draining lymph nodes via CCR2 and locally modulate the immune response

Qods Lahmar, Elio Schouppe, Yannick Morias, Eva Van Overmeire, Patrick De Baetselier, Kiavash Movahedi, Damya Laoui, Adelaida Sarukhan, Jo A Van Ginderachter

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Efficient priming of anti-tumor T cells requires the uptake and presentation of tumor antigens by immunogenic dendritic cells (DCs) and occurs mainly in lymph nodes draining the tumor (tdLNs). However, tumors expand and activate myeloid-derived suppressor cells (MDSCs) that inhibit CTL functions by several mechanisms. While the immune-suppressive nature of the tumor microenvironment is largely documented, it is not known whether similar immune-suppressive mechanisms operate in the tdLNs. In this study, we analyzed MDSC characteristics within tdLNs. We show that, in a metastasis-free context, MO-MDSCs are the dominant MDSC population within tdLNs, that they are highly suppressive and that tumor proximity enhances their recruitment to tdLN via a CCR2/CCL2-dependent pathway. Altogether our results uncover a mechanism by which tumors evade the immune system that involves MDSC-mediated recruitment to the tdLN and the inhibition of T-cell activation even before reaching the highly immunosuppressive tumor microenvironment.

Original languageEnglish
Article number104296
Number of pages8
JournalCellular Immunology
Volume362
Early online date30 Jan 2021
DOIs
Publication statusPublished - Apr 2021

Bibliographical note

Copyright © 2021 Elsevier Inc. All rights reserved.

Keywords

  • CCR2
  • MO-MDSC
  • Tumor-draining lymph node

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