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Among them, the PTEN/PI3K/mTOR signaling pathway has been shown to be involved in macrophage repolarization, such as porous hollow iron oxide nanoparticles PHNP@3-MA loaded with P13K small molecule inhibitors modified with mannose can target TAMs, and PHNPs combined with 3-MA can activate the inflammatory factor NF-B p65 of macrophages thereby converting TAMs into pro-inflammatory M1 macrophages, activating immune responses and inhibiting tumor growth in vivo ( 52, 53), such as the mRNA encoding BisCCL2/5i encapsulated in a lipid nanoparticle platform can block both CCL2 and CCL5 signaling thereby significantly inducing TAMs to the anti-tumor M1 phenotype polarization and reversing immunosuppression in the TME (54)

The CYP2R1 gene is located on chromosome 11p15.2 and is composed of 9 exons that generate six alternatively spliced mRNAs encoding three distinct protein isoforms

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