Frontiers in Immunology (Dec 2022)

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

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

DOI
https://doi.org/10.3389/fimmu.2022.1003975
Journal volume & issue
Vol. 13

Abstract

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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.

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