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

• Published in: Frontiers in immunology 2022-12, Vol.13, p.1003975-1003975
• Main Authors: 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
• Format: Article
• Language: English
• Subjects: Animals; extravasation; F11R; Immunology; Inflammation - metabolism; JAM-1; JAM-A; Junctional Adhesion Molecule A; Mice; monocyte; Monocytes - metabolism; Myeloid Cells - metabolism; Tumor Microenvironment - genetics
• ISSN: 1664-3224; 1664-3224
• DOI: 10.3389/fimmu.2022.1003975

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.