<p>Schematic overview mechanism of Ewing sarcoma cells shaping the immune microenvironment into an immunosuppressive niche. (<a href="#bib1" target="_blank">1</a>) Immunomodulatory interactions between Ewing sarcoma cells and myeloid cells induce polarization of macrophages to an immunosuppressive, M2-like, phenotype and induce tolerogenic DCs. (<a href="#bib2" target="_blank">2</a>) Immunosuppressive macrophage interacts with T cell, where, for example, TIGIT–NECTIN2 interactions leads to the inhibition of T-cell activation resulting in a suppressed/dysfunctional T cell. (<a href="#bib3" target="_blank">3</a>) Tolerogenic DC interacts with naïve T cells but is lacking expression of costimulatory molecules, important for T-cell priming, resulting in a tolerogenic T cell. (<a href="#bib4" target="_blank">4</a>) T cell interacts with Ewing sarcoma cell, but because of it tolerogenic state the T cell is unable to activate, produce cytokines, and proliferate which are essential for cancer cell killing. Image created using BioRender.</p>
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