肿瘤微环境
免疫疗法
促炎细胞因子
趋化因子
免疫系统
免疫学
癌症免疫疗法
癌症研究
CD8型
免疫检查点
细胞毒性T细胞
医学
T细胞
细胞因子
生物
炎症
体外
生物化学
作者
Zhiyong Cai,Jinbo Chen,Zheng-Zheng Yu,Huihuang Li,Zhi Li,Dingshan Deng,Jinhui Liu,Chunliang Chen,Chunyu Zhang,Zhenyu Ou,Minfeng Chen,Jiao Hu,Xiongbing Zu
标识
DOI:10.1002/advs.202207155
摘要
To improve response rate of monotherapy of immune checkpoint blockade (ICB), it is necessary to find an emerging target in combination therapy. Through analyzing tumor microenvironment (TME)-related indicators, it is validated that BCAT2 shapes a noninflamed TME in bladder cancer. The outcomes of multiomics indicate that BCAT2 has an inhibitory effect on cytotoxic lymphocyte recruitment by restraining activities of proinflammatory cytokine/chemokine-related pathways and T-cell-chemotaxis pathway. Immunoassays reveal that secretion of CD8+ T-cell-related chemokines keeps a robust negative correlation with BCAT2, generating a decreasing tendency of CD8+ T cells around BCAT2+ tumor cells from far to near. Cotreatment of BCAT2 deficiency and anti-PD-1 antibody has a synergistic effect in vivo, implying the potential of BCAT2 in combination therapy. Moreover, the value of BCAT2 in predicting efficacy of immunotherapy is validated in multiple immunotherapy cohorts. Together, as a key molecule in TME, BCAT2 is an emerging target in combination with ICB and a biomarker of guiding precision therapy.
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