Identification of Surface Markers and Functional Characterization of Myeloid Derived Suppressor Cell-Like Adherent...

Myeloid-derived suppressor cell (MDSC)-like adherent cells (MLACs) are a recently identified CD11b⁺ F4/80^- myeloid cell subset that can infiltrate tumors early in development and promote their growth. Because of these functions, MLACs play an important role in establishing an immunosuppressive tumor microenvironment (TME). However, the lack of MLAC-specific markers has hampered further characterization of this cell type. This study identifies the gene signature of MLACs by analyzing RNA-sequencing (RNA-seq) and public single-cell RNA-seq data, revealing that MLACs are an independent cell population that are distinct from other intratumoral myeloid cells. After combining proteome analysis of membrane proteins with RNA-seq data, H2-Ab1 and CD11c are indicated as marker proteins that can support the isolation of MLAC subsets from CD11b⁺ F4/80^- myeloid cells by fluorescence-activated cell sorting. The CD11b⁺ F4/80^- H2-Ab1⁺ and CD11b⁺ F4/80^- CD11c⁺ MLAC subsets represent approximately half of the MLAC population that is isolated based on their adhesion properties and possess gene signatures and functional properties similar to those of the MLAC population. Additionally, membrane proteome analysis suggests that MLACs express highly heterogeneous surface proteins. This study facilitates an integrated understanding of heterogeneous intratumoral myeloid cells, as well as the molecular and cellular details of the development of an immunosuppressive TME.