非常规 T 细胞在泌尿系统肿瘤中:能抓住就抓住
Unconventional T cells in urological cancers: catch them if you can.
肿瘤细胞治疗研究
英文原题:Tumor B-cell infiltration in platinum-treated advanced muscle-invasive urothelial carcinoma.
Tumor B-cell infiltration in platinum-treated advanced muscle-invasive urothelial carcinoma.
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铂类化疗是晚期尿路上皮癌的标准治疗选择,但能证明其获益的生物标志物有限。我们检验了肿瘤微环境,尤其是B细胞浸润,是否能预测铂类化疗后的总生存期。来自三个队列的189例接受顺铂或卡铂为基础方案治疗的患者,其治疗前肿瘤接受了批量转录组分析。通过基因表达推断免疫细胞浸润和多细胞群落,并使用队列特异性多变量模型和荟萃分析将其与总生存期相关联。较高的淋巴细胞浸润与较长的总生存期相关(风险比0.34,95%置信区间0.16-0.72),这一关联由B细胞和记忆B细胞驱动(风险比0.19,95%置信区间0.05-0.75)。这些关联仅限于顺铂治疗的患者,并且在具有促炎性B细胞富集群落和一致的B细胞基因表达特征的肿瘤中最为显著。相比之下,较高的髓系细胞浸润与较短的总生存期相关。肿瘤微环境中治疗前B细胞富集识别出一个在接受铂类化疗,尤其是顺铂治疗的患者中与改善的总生存期相关的亚群,支持以B细胞为重点的生物标志物开发以及尿路上皮癌中三级淋巴结构的空间特征描述。
Platinum chemotherapy is a standard therapeutic choice for advanced urothelial cancer, but biomarkers demonstrating its benefits are limited.
We tested whether the tumor microenvironment, particularly B-cell infiltration, could predict overall survival after platinum chemotherapy. Pretreatment tumors from 189 patients in three cohorts treated with cisplatin- or carboplatin-based regimens underwent bulk transcriptome profiling. Immune cell infiltration and multicellular communities were inferred from gene expression and associated with overall survival using cohort-specific multivariable models and meta-analysis. Higher lymphocyte infiltration was associated with longer overall survival (hazard ratio 0. 34, 95% confidence interval 0. 16-0. 72), driven by B cells and memory B cells (hazard ratio 0.
19, 95% confidence interval 0. 05-0. 75). These associations were confined to cisplatin-treated patients and were strongest in tumors with a pro-inflammatory B-cell-rich community and concordant B-cell gene expression signatures. In contrast, higher myeloid infiltration was associated with shorter overall survival.
Pretreatment B-cell enrichment in the tumor microenvironment identified a subset associated with improved overall survival among patients receiving platinum chemotherapy, particularly cisplatin, supporting B-cell-focused biomarker development and spatial characterization of tertiary lymphoid structures in urothelial cancer.
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