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B7-H3 表达在转移性肾细胞癌中的预后价值及其对免疫治疗反应的影响。

Prognostic value of B7-H3 expression in metastatic renal cell carcinoma and its impact on immunotherapy response.

机构信息

Department of Medical Oncology, Dokuz Eylul University Faculty of Medicine, Izmir, Turkey.

Department of Pathology, Dokuz Eylul University Faculty of Medicine, Izmir, Turkey.

出版信息

BMC Cancer. 2024 Nov 29;24(1):1471. doi: 10.1186/s12885-024-13238-x.

Abstract

BACKGROUND

Renal cell carcinoma (RCC) is characterised by its immunogenic and proangiogenic nature and its resistance to conventional therapies. The advent of immune checkpoint inhibitors (ICIs) and tyrosine kinase inhibitors (TKIs) has significantly improved patient survival, but resistance to these treatments remains a challenge. B7-H3, a potential immune checkpoint, has been implicated in modulating the tumour microenvironment and immune escape mechanisms in RCC.

METHODS

Immunohistochemical analysis of B7-H3 expression was performed in 84 metastatic RCC patients. Tissue microarrays and separate sections of formalin-fixed paraffin-embedded tissue were used for immunohistochemical staining. Membranous staining of the tumor cells was scored and statistical analyses were performed to assess the correlation between B7-H3 expression and treatment outcome.

RESULTS

B7-H3 expression was absent in 31% of patients, while 33.3% had a score of 1+, 31% had 2+, and 4.8% had 3+. High B7-H3 expression correlated with poorer OS (20 months vs. 45 months, p = 0.012). In patients receiving nivolumab, those with high B7-H3 expression had shorter PFS (2 months vs. 8 months, p = 0.037) and OS (17 months vs. 51 months, p = 0.01). B7-H3 expression was the only factor significantly affecting PFS and OS in multivariate analysis.

CONCLUSION

High B7-H3 expression is associated with poorer survival outcomes and reduced response to nivolumab in metastatic RCC patients. B7-H3 may serve as a predictive biomarker for immunotherapy response. Future studies should explore targeting B7-H3 in combination with existing therapies to enhance treatment efficacy.

摘要

背景

肾细胞癌(RCC)的特点是免疫原性和促血管生成特性以及对常规治疗的耐药性。免疫检查点抑制剂(ICIs)和酪氨酸激酶抑制剂(TKIs)的出现显著提高了患者的生存率,但这些治疗的耐药性仍然是一个挑战。B7-H3 是一种潜在的免疫检查点,已被认为参与调节 RCC 中的肿瘤微环境和免疫逃逸机制。

方法

对 84 例转移性 RCC 患者进行 B7-H3 表达的免疫组织化学分析。使用组织微阵列和福尔马林固定石蜡包埋组织的单独切片进行免疫组织化学染色。对肿瘤细胞的膜染色进行评分,并进行统计学分析,以评估 B7-H3 表达与治疗结果之间的相关性。

结果

31%的患者 B7-H3 表达缺失,33.3%的患者评分 1+,31%的患者评分 2+,4.8%的患者评分 3+。高 B7-H3 表达与较差的 OS 相关(20 个月与 45 个月,p=0.012)。在接受nivolumab 治疗的患者中,B7-H3 高表达者的 PFS(2 个月与 8 个月,p=0.037)和 OS(17 个月与 51 个月,p=0.01)更短。B7-H3 表达是多变量分析中唯一显著影响 PFS 和 OS 的因素。

结论

高 B7-H3 表达与转移性 RCC 患者的生存结局较差和对 nivolumab 反应降低相关。B7-H3 可能是免疫治疗反应的预测生物标志物。未来的研究应探索靶向 B7-H3 与现有治疗相结合,以提高治疗效果。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/13e8/11606205/6692a316f880/12885_2024_13238_Fig1_HTML.jpg

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