Novel adherent CD11b+ Gr-1+ tumor-infiltrating cells initiate an immunosuppressive tumor microenvironment

Abstract

The immunosuppressive tumor microenvironment is a hallmark of cancer. Myeloid-derived suppressor cells (MDSCs) are CD11b⁺ Gr-1⁺ tumor-infiltrating immature myeloid cells that strongly mediate tumor immunosuppression. The CD11b⁺ Gr-1⁺ cells are a heterogeneous cell population, and the impacts of each subpopulation on tumor progression are not yet completely understood. In the present study, we identified a novel subpopulation of CD11b⁺ Gr-1⁺ cells from murine lung carcinoma tumors according to their strongly adherent abilities. Although strong adherent activity is a unique property of macrophages, their marker expression patterns are similar to those of MDSCs; thus, we named this novel subpopulation MDSC-like adherent cells (MLACs). Unlike known MDSCs, MLACs lack the ability to suppress cytotoxic T lymphocytes and differentiate into tumor-associated macrophages (TAMs), but could still directly facilitate tumor growth and angiogenesis through secreting CCL2, CXCL1/2/5, PAI-1, MMPs, and VEGFA. Furthermore, MLACs recruited MDSCs via the secretion of CCL2/5 and CXCL1/2/5, thereby enhancing the immunosuppressive tumor microenvironment and promoting TAMs-mediated tumor progression. Our findings suggest that MLACs may function as an initiator of the immunosuppressive tumor microenvironment and highlight a new therapeutic target to prevent the onset or delay malignant progression.