BCAT2 Shapes a Noninflamed Tumor Microenvironment and Induces Resistance to Anti‐PD‐1/PD‐L1 Immunotherapy by Negatively Regulating Proinflammatory Chemokines and Anticancer Immunity

• DOI: 10.1002/advs.202207155
• Publication Date: 2023-01-16T05:09:20Z
• Authors: 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
• Keywords: Proinflammatory cytokine; Cancer Immunotherapy; Immune checkpoint

Abstract To improve response rate of monotherapy immune checkpoint blockade (ICB), it is necessary to find an emerging target in combination therapy. Through analyzing tumor microenvironment (TME)‐related indicators, validated that BCAT2 shapes a noninflamed TME bladder cancer. The outcomes multiomics indicate has inhibitory effect on cytotoxic lymphocyte recruitment by restraining activities proinflammatory cytokine/chemokine‐related pathways and T‐cell‐chemotaxis pathway. Immunoassays reveal secretion CD8 + T‐cell‐related chemokines keeps robust negative correlation with BCAT2, generating decreasing tendency T cells around from far near. Cotreatment deficiency anti‐PD‐1 antibody synergistic vivo, implying the potential Moreover, value predicting efficacy immunotherapy multiple cohorts. Together, as key molecule TME, ICB biomarker guiding precision