背景：膀胱癌（BCa）患者对免疫治疗的敏感性仍然较低。随着蛋白质甲基化在肿瘤发生和发展中作用越来越明确，值得研究脯氨酸N-甲基转移酶SET结构域含7（SETD7）在BCa进展和免疫逃避中的作用。方法：分析脯氨酸甲基转移酶家族与BCa患者预后或免疫治疗敏感性之间的相关性，由于SETD7的表达与生存数据或免疫治疗敏感性之间的显著相关性，它被筛选出来。探究BCa组织和细胞系中SETD7的表达。通过增殖和迁移实验研究SETD7的功能。通过分析SETD7表达与肿瘤微环境（TME）相关指标之间的关联性来验证SETD7在BCa免疫逃避中的作用。进一步通过进行BCa细胞-CD8+ T细胞共培养实验和人类免疫重建NOG小鼠（HuNOG小鼠）的肿瘤发生实验来证实结果。采用生物信息学预测、共沉淀、qRT-PCR和西方印迹验证SETD7/STAT3/PD-L1级联反应。结果：SETD7在BCa中高度表达，与高组织学分级和更差预后呈正相关。SETD7促进BCa细胞的增殖和迁移。生物信息学分析、体外共培养和体内肿瘤发生实验结果表明，SETD7能抑制BCa TME中CD8+ T细胞的化学趋化和细胞毒性。从机制上来看，生物信息学分析、共沉淀实验、qRT-PCR和西方印迹结果表明，SETD7能通过结合和促进STAT3来增加PD-L1的表达。结论：总体而言，SETD7提示BCa细胞预后不良，促进BCa的进展和免疫逃避。它具有作为BCa诊断和治疗新指标的巨大潜力，尤其是免疫治疗。© 作者.

Background: The immunotherapy sensitivity of patients with bladder cancer (BCa) remains low. As the role of protein methylation in tumorigenesis and development becomes clearer, the role of lysine N-methyltransferase SET domain containing 7 (SETD7) in the progression and immune escape of BCa is worth studying. Methods: The correlation between lysine methyltransferase family and prognosis or immunotheray sensitivity of BCa patients were analyzed, and SETD7 was screened out because of the significant correlation between its expression and survival data or immunotherapy sensitivity. The expression of SETD7 in BCa tissues and cell lines were explored. The functions of SETD7 were investigated by proliferation and migration assays. The role of SETD7 in BCa immune escape was validated by analyzing the correlation between SETD7 expression and tumor microenvironment (TME)-related indicators. The results were further confirmed by conducting BCa cell-CD8+ T cell co-culture assays and tumorigenesis experiment in human immune reconstitution NOG mice (HuNOG mice). Bioinformatic prediction, CO-IP, qRT-PCR, and western blot were used to validate the SETD7/STAT3/PD-L1 cascade. Results: SETD7 was highly expressed in BCa, and it was positively associated with high histological grade and worse prognosis. SETD7 promoted the proliferation and migration of BCa cells. The results of bioinformatics, in vitro co-culture, and in vivo tumorigenesis assays showed that SETD7 could inhibit the chemotoxis and cytotoxicity of CD8+ T cells in BCa TME. Mechanistically, bioinformatics analysis, CO-IP assay, qRT-PCR, and western blot results indicated that SETD7 could increase the expression of PD-L1 via binding and promoting STAT3. Conclusions: Taken together, SETD7 indicated poor prognosis and promoted the progression and immune escape of BCa cells. It has great potential to act as a new indicator for BCa diagnosis and treatment, especially immunotherapy.© The author(s).