为了鉴定CD8+T细胞相关的分子簇并建立一个新的基因签名来预测膀胱癌（BCa）免疫治疗的预后和疗效。我们从癌基因组图谱（TCGA）和GEO数据库中获得了BCa样本的转录组和临床数据。通过CIBERSORT算法和相关分析筛选出CD8+T细胞相关的基因。采用共识聚类分析来识别CD8+T细胞相关的分子簇。通过单因素Cox回归分析和Lasso回归分析构建了一个新的CD8+T细胞相关的预后模型。内外部验证并在实际队列中验证了模型的有效性。最后，进行了初步的实验验证以验证SH2D2A在膀胱癌中的生物学功能。 共筛选出52个与CD8+T细胞相关的预后基因，并发现了两个具有显著不同免疫细胞浸润、预后和临床特征的分子簇。然后构建了一个新的CD8+T细胞相关的预后模型。高风险评分的患者在训练、测试、整个TCGA和验证队列中均显示了显著更差的总体生存。在这四个队列中的AUC分别为0.766、0.725、0.739和0.658。亚组分析表明，新的预后模型对选择高风险患者具有强大的临床应用价值。最后，我们确认低风险组的患者可能更有益于免疫治疗或化疗，并在实际的免疫治疗队列中验证了预后模型。初步实验表明，SH2D2A能够减轻BCa细胞的增殖、迁移和侵袭。 成功鉴定了CD8+T细胞相关的分子簇，建立了一个具有出色预测性能的新的CD8+T细胞相关的预后模型，可预测BCa的生存率和免疫治疗效果。© 2023. 由作者独家许可 Springer Nature Switzerland AG。

To identify CD8+ T cell-related molecular clusters and establish a novel gene signature for predicting the prognosis and efficacy of immunotherapy in bladder cancer (BCa).Transcriptome and clinical data of BCa samples were obtained from the Cancer Genome Atlas (TCGA) and GEO databases. The CD8+ T cell-related genes were screened through the CIBERSORT algorithm and correlation analysis. Consensus clustering analysis was utilized to identified CD8+ T cell-related molecular clusters. A novel CD8+ T cell-related prognostic model was developed using univariate Cox regression analysis and Lasso regression analysis. Internal and external validations were performed and the validity of the model was validated in a real-world cohort. Finally, preliminary experimental verifications were carried out to verify the biological functions of SH2D2A in bladder cancer.A total of 52 CD8+ T cell-related prognostic genes were screened and two molecular clusters with notably diverse immune cell infiltration, prognosis and clinical features were developed. Then, a novel CD8+ T cell-related prognostic model was constructed. The patients with high-risk scores exhibited a significantly worse overall survival in training, test, whole TCGA and validating cohort. The AUC was 0.766, 0.725, 0.739 and 0.658 in the four cohorts sequentially. Subgroup analysis suggested that the novel prognostic model has a robust clinical application for selecting high-risk patients. Finally, we confirmed that patients in the low-risk group might benefit more from immunotherapy or chemotherapy, and validated the prognostic model in a real-world immunotherapy cohort. Preliminary experiment showed that SH2D2A was capable of attenuating proliferation, migration and invasion of BCa cells.CD8+ T cell-related molecular clusters were successfully identified. Besides, a novel CD8+ T cell-related prognostic model with an excellent predictive performance in predicting survival rates and immunotherapy efficacy of BCa was developed.© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.