Junctional adhesion molecule-A is dispensable for myeloid cell recruitment and diversification in the tumor microenvironment

Máté Kiss, Els Lebegge, Aleksandar Murgaski, Helena Van Damme, Daliya Kancheva, Jan Brughmans, Isabelle Scheyltjens, Ali Talebi, Robin Maximilian Awad, Yvon Elkrim, Pauline M R Bardet, Sana M Arnouk, Cleo Goyvaerts, Johan Swinnen, Frank Aboubakar Nana, Jo A Van Ginderachter, Damya Laoui

Research output: Contribution to journalArticlepeer-review

Abstract

Junctional adhesion molecule-A (JAM-A), expressed on the surface of myeloid cells, is required for extravasation at sites of inflammation and may also modulate myeloid cell activation. Infiltration of myeloid cells is a common feature of tumors that drives disease progression, but the function of JAM-A in this phenomenon and its impact on tumor-infiltrating myeloid cells is little understood. Here we show that systemic cancer-associated inflammation in mice enhanced JAM-A expression selectively on circulating monocytes in an IL1β-dependent manner. Using myeloid-specific JAM-A-deficient mice, we found that JAM-A was dispensable for recruitment of monocytes and other myeloid cells to tumors, in contrast to its reported role in inflammation. Single-cell RNA sequencing revealed that loss of JAM-A did not influence the transcriptional reprogramming of myeloid cells in the tumor microenvironment. Overall, our results support the notion that cancer-associated inflammation can modulate the phenotype of circulating immune cells, and we demonstrate that tumors can bypass the requirement of JAM-A for myeloid cell recruitment and reprogramming.

Original languageEnglish
Article number1003975
Number of pages14
JournalFrontiers in Immunology
Volume13
DOIs
Publication statusPublished - 1 Dec 2022

Bibliographical note

Funding Information:
MK, AM, HVD, EL, SA, and PB are supported by doctoral grants from Research Foundation Flanders (FWO, grant numbers 1S23316N, 1S16718N, 1S24117N, 1S67419N, 1S78120N, 1154720N). MK and AM are supported by doctoral grants from Kom op Tegen Kanker (Stand up to Cancer), the Flemish Cancer Society. DL is supported by grants from FWO (12Z1820N), Kom op Tegen Kanker and Vrije Universiteit Brussel. JVG is supported by FWO, Kom op Tegen Kanker, Stichting tegen kanker and Vrije Universiteit Brussel.

Publisher Copyright:
Copyright © 2022 Kiss, Lebegge, Murgaski, Van Damme, Kancheva, Brughmans, Scheyltjens, Talebi, Awad, Elkrim, Bardet, Arnouk, Goyvaerts, Swinnen, Nana, Van Ginderachter and Laoui.

Copyright:
Copyright 2022 Elsevier B.V., All rights reserved.

Keywords

  • Mice
  • Animals
  • Junctional Adhesion Molecule A
  • Tumor Microenvironment/genetics
  • Myeloid Cells/metabolism
  • Monocytes/metabolism
  • Inflammation/metabolism

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