AUTHOR=Kiss Máté , Lebegge Els , Murgaski Aleksandar , Van Damme Helena , Kancheva Daliya , Brughmans Jan , Scheyltjens Isabelle , Talebi Ali , Awad Robin Maximilian , Elkrim Yvon , Bardet Pauline M. R. , Arnouk Sana M. , Goyvaerts Cleo , Swinnen Johan , Nana Frank Aboubakar , Van Ginderachter Jo A. , Laoui Damya TITLE=Junctional adhesion molecule-A is dispensable for myeloid cell recruitment and diversification in the tumor microenvironment JOURNAL=Frontiers in Immunology VOLUME=13 YEAR=2022 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2022.1003975 DOI=10.3389/fimmu.2022.1003975 ISSN=1664-3224 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.