程序性死亡 1 阻断（替雷利珠单抗）已被批准用于治疗转移性尿路上皮癌，但未作为肌层浸润性膀胱癌（MIBC）新辅助治疗的一部分。在这项多中心单臂试验 (ChiCTR2000037670) 中，65 名患有 cT2-4aN0M0 MIBC 的参与者接受了新辅助吉西他滨-顺铂联合替雷利珠单抗治疗；其中 57 人接受了根治性膀胱切除术 (RC)。主要终点病理完全缓解 (pCR) 率为 50.9%（29/57，95% 置信区间 (CI) 37.3-64.4%），病理降期（次要终点）率为 75.4%（43/57，95%）接受 RC 的参与者的 CI 62.2-85.9%）。基因组和转录组分析揭示了三种 MIBC 分子亚型 (S)：具有激活的细胞周期途径的 S1（免疫沙漠）、具有激活的转化生长因子-β 途径的 S2（免疫排除）和具有上调的干扰素的 S3（免疫炎症） -α和干扰素-γ反应。事后分析显示 pCR 率为 16% (3/19, S1)、77% (10/13, S2) 和 80% (12/15, S3) (P = 0.006)。总之，用于 MIBC 的新辅助吉西他滨-顺铂联合替雷利珠单抗可提高 pCR 率。© 2024。作者获得 Springer Nature America, Inc. 的独家许可。

Programmed death 1 blockade (tislelizumab) has been approved for metastatic urothelial carcinoma but not as part of neoadjuvant therapy for muscle-invasive bladder cancer (MIBC). In this multicenter single-arm trial (ChiCTR2000037670), 65 participants with cT2-4aN0M0 MIBC received neoadjuvant gemcitabine-cisplatin plus tislelizumab; 57 of them underwent radical cystectomy (RC). The primary endpoint of pathologic complete response (pCR) rate was 50.9% (29/57, 95% confidence interval (CI) 37.3-64.4%) and the pathologic downstaging (secondary endpoint) rate was 75.4% (43/57, 95% CI 62.2-85.9%) in participants undergoing RC. Genomic and transcriptomic analyses revealed three MIBC molecular subtypes (S): S1 (immune-desert) with activated cell-cycle pathway, S2 (immune-excluded) with activated transforming growth factor-β pathway and S3 (immune-inflamed) with upregulated interferon-α and interferon-γ response. Post hoc analysis showed pCR rates of 16% (3/19, S1), 77% (10/13, S2) and 80% (12/15, S3) (P = 0.006). In conclusion, neoadjuvant gemcitabine-cisplatin plus tislelizumab for MIBC was compatible with an enhanced pCR rate.© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.