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SCI 5 November 2024 Overcoming tyrosine kinase inhibitor resistance in lung cancer brain metastasis with CTLA4 blockade (Cancer Cell, IF: 48.8) Fu M, Zhao J, Zhang L, et al: Overcoming tyrosine kinase inhibitor resistance in lung cancer brain metastasis with CTLA4 blockade. Cancer Cell S1535-6108(24)00360-X, 2024 Abstract 摘要 Lung cancer brain metastasis (LCBM) poses a significant clinical challenge due to acquired resistance to tyrosine kinase inhibitor (TKI) treatment. To elucidate its underlying mechanisms, we employed single-cell RNA sequencing analysis on surgically obtained LCBM samples with diverse genetic backgrounds and TKI treatment histories. Our study uncovers that TKI treatment elevates the immune checkpoint CTLA4 expression in T cells, promoting an immune-suppressive microenvironment. This immunomodulation is initiated by tumor-derived HMGB1 in response to TKIs. In LCBM syngeneic murine models with TKI-sensitive or TKI-resistant EGFR mutations, combining CTLA4 block
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