Elevated pre-existing lymphocytic infiltrates in tumour stroma predict poor prognosis in resectable urothelial carcinoma of the bladder
Elevated pre-existing lymphocytic infiltrates in tumour stroma predict poor prognosis in resectable urothelial carcinoma of the bladder
复制标题
肿瘤基质中预先存在的淋巴细胞浸润升高预示可切除膀胱尿路上皮癌的预后不良
DOI：
10.1111/his.13807
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发表时间：
2019
期刊：
影响因子：
6.4
通讯作者：
Lin Tianxin
中科院分区：
文献类型：
--
作者：
Wang Bo;Xie Shujie;Bi Junming;Liu Zhuowei;Zeng Hong;Huang Hao;Xue Miaoxin;He Zhihua;Yang Meihua;Yu Hao;Huang Jian;Lin Tianxin
AimsLymphocytic infiltrates are predominantly distributed in the tumour stroma, and represents the tumour‐related immune response. The aim of this study was to elucidate the prognostic value of stromal lymphocytic infiltrates (SLI) in resectable urothelial carcinoma of the bladder (UCB).Methods and resultsThe prognostic significance of SLI in UCB was assessed in a discovery cohort (n= 226; 60 deaths) and in a validation cohort (n= 417; 103 deaths). SLI was categorised into intense (≥50% SLI) and non‐intense (<50% SLI). A multivariable Cox model was used to analyse the associations of SLI score with overall survival (OS) and disease‐free survival. Immunofluorescence staining was used to examine the composition and phenotypes of SLI. The median follow‐up times were 58.1 and 64.9 months in the discovery and validation cohorts, respectively. SLI was intense in 38.1% of patients in the discovery cohort and in 20.9% of patients in the validation cohort (P< 0.001). SLI score had independent prognostic value for OS [hazard ratio (HR) 2.132;P= 0.016] and disease‐specific survival (DSS) (HR 1.952;P= 0.04) in the discovery cohort, which was confirmed in the validation cohort (OS: HR 1.636;P= 0.023; DSS: HR 1.627;P= 0.029). SLI score was positively associated with histological grade, tumour stage and lymph node status in both cohorts. Moreover, in the stroma, SLI displayed a broad spectrum of inhibitory immune cells, by expressing several major immune checkpoint molecules, i.e. programmed cell death protein 1, programmed death‐ligand 1, indoleamine 2,3‐dioxygenase, and T‐cell immunoglobulin and mucin domain 3.ConclusionIntense pre‐existing SLI was validated as a reliable marker of poorer prognosis for survival in UCB patients, which may add to the prognostic significance of the TNM classification.
