Zhiyong Cai, Jinbo Chen, Zhengzheng Yu, Huihuang Li, Zhi Liu, Dingshan Deng, Jinhui Liu, Chunliang Chen, Chunyu Zhang, Zhenyu Ou, Minfeng Chen, Jiao Hu, Xiongbing Zu
Advanced science (Weinheim, Baden-Wurttemberg, Germany) 2023 MarTo 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. © 2023 The Authors. Advanced Science published by Wiley-VCH GmbH.
Zhiyong Cai, Jinbo Chen, Zhengzheng Yu, Huihuang Li, Zhi Liu, Dingshan Deng, Jinhui Liu, Chunliang Chen, Chunyu Zhang, Zhenyu Ou, Minfeng Chen, Jiao Hu, Xiongbing Zu. BCAT2 Shapes a Noninflamed Tumor Microenvironment and Induces Resistance to Anti-PD-1/PD-L1 Immunotherapy by Negatively Regulating Proinflammatory Chemokines and Anticancer Immunity. Advanced science (Weinheim, Baden-Wurttemberg, Germany). 2023 Mar;10(8):e2207155
PMID: 36642843
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