Anti-SLC7A11 monoclonal antibody Inhibits Tumor Progression through a Janus-faced Effect on CD4+ and CD8+ T Cells in Colorectal Cancer [RNA-seq]

SLC7A11 is aberrantly overexpressed in numerous solid tumors, including colorectal cancer (CRC), where it serves as a key regulator of cystine import and ferroptosis. However, its therapeutic potential and feasible targeting strategies remain less well understood. Our findings reveal that elevated SLC7A11 expression is critical for the activation of regulatory T cells and is associated with advanced tumor grade, lymphatic metastasis, and poor prognosis in CRC patients. A monoclonal antibody that blocks the transporter function of SLC7A11 induces apoptosis across multiple cancer cell types and demonstrates significant therapeutic efficacy in preclinical mouse models of colon cancer. Additionally, inhibition of SLC7A11 reprograms the tumor immune microenvironment, transforming it from a 'cold' to a more immunogenic state by suppressing regulatory T cell activation. These results highlight the dual role of SLC7A11 in modulating CD4+ and CD8+ T cell responses, positioning SLC7A11 as a crucial orchestrator of tumor immune evasion and a promising therapeutic target.