Junctional Adhesion Molecule-A is dispensable for myeloid cell recruitment and diversification in the tumor microenvironment

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 macrophage activation. Myeloid cell infiltration is a common feature of tumors that drives disease progression, but the function of JAM-A in this phenomenon and its impact on cancer-associated myeloid cells is little understood. Here we show that systemic cancer-induced inflammation in mice enhanced JAM-A expression in an IL1ß-dependent manner specifically on circulating monocytes. However, 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 the loss of JAM-A did not influence the transcriptional reprogramming of tumor-infiltrating myeloid cells. 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. Overall design: Sorted 7-AAD-CD45+ cells from subcutaneous Lewis lung carcinoma (LLC) tumors of myeloid-specific JAM-A knockout mice (F11rfl/fl LysM-Cre+) and their wild-type littermates (F11rfl/fl). Three mice per genotype were pooled for the library preparation.