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The Macrophage scavenger receptor 1 (MSR1)–Integral membrane protein 2A (ITM2A) interaction is a newly identified signaling axis that plays a critical role in the regulation of the tumor microenvironment [1]. Macrophage Scavenger Receptor 1 (MSR1), also known as CD204, is a transmembrane protein primarily expressed on macrophages that typically functions in the clearance of modified lipids and apoptotic cells [2, 4]. Recent research has identified Integral Membrane Protein 2A (ITM2A) as a specific functional ligand for MSR1, particularly in the context of various solid tumors [1, 3]. When ITM2A is secreted or expressed by tumor cells, it binds to MSR1 on tumor-associated macrophages (TAMs), triggering intracellular signaling that promotes their polarization into an immunosuppressive M2 phenotype [1]. This M2 polarization facilitates tumor evasion from the immune system, promotes angiogenesis, and supports metastatic progression [1, 4]. Consequently, the MSR1–ITM2A interaction has emerged as a promising therapeutic target for cancer immunotherapy. Therapeutic strategies currently under investigation involve the use of monoclonal antibodies to block this interaction, thereby preventing M2 polarization and restoring the anti-tumor activity of macrophages [1].
Blockade of the protein-protein interaction between ITM2A and MSR1 to inhibit pro-tumorigenic M2 macrophage polarization and enhance anti-tumor immunity.
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