PD-L1 (B7-H1) expression by urothelial carcinoma of bladder and BCG-induced granulomata - Associations with localized stage progression
PD-L1 (B7-H1) expression by urothelial carcinoma of bladder and BCG-induced granulomata - Associations with localized stage progression
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DOI：
10.1002/cncr.22588
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发表时间：
2007-04-15
期刊：
影响因子：
6.2
通讯作者：
Kwon, Eugene D.
中科院分区：
文献类型：
--
作者：
Inman, Brant A.;Sebo, Thomas J.;Kwon, Eugene D.
背景PD-L1（程序性死亡配体1，B7-H1）是一种细胞表面糖蛋白，可损害T细胞功能。PD-L1在多种人类恶性肿瘤中异常表达，并且已被证明在肾癌患者中具有非常不利的预后。PD-L1作为膀胱尿路上皮癌（UC）局部阶段进展的机制进行了评估。使用免疫组织化学，在280例膀胱高危UC队列中评价PD-L1表达。使用有序逻辑回归将PD-L1建模为膀胱癌分期的预测因子。其他被评估为潜在混杂因素的协变量包括年龄、性别、肿瘤分级和淋巴细胞浸润。此外，PD-L1被评估为接受这种治疗的高风险非肌肉浸润性肿瘤亚组中卡介苗（BCG）失败的潜在机制。在7%的pTa、16%的pT 1、23%的pT 2、30%的pT 3/4和45%的原位癌（CIS）肿瘤中观察到PD-L1表达。PD-L1表达与高级别肿瘤（比值比[OR] = 2.4，P = 0.009）和单核细胞肿瘤浸润（OR = 5.5，P = 0.004）相关。我们观察到，该队列中阶段进展的关键决定因素是世界卫生组织/国际泌尿病理学会（WHO/ISUP）高级别肿瘤病理学（OR 4.77，95%置信区间[CI]：2.73-8.34; P < .001）和PD-L1表达（OR = 2.20，P = .012）。在BCG治疗失败的12例患者中，11例患者的BCG诱导的膀胱肉芽肿中发现PD-L1表达非常丰富。总的来说，这些数据表明，肿瘤PD-L1可能促进UC的局部分期进展，并通过中和通常防止癌症从上皮侵入膀胱肌肉组织的T细胞来减弱对BCG免疫治疗的反应。
BACKGROUND. PD-L1 (programmed death ligand 1, B7-H1) is a cell surface glycoprotein that can impair T-cell function. PD-L1 is aberrantly expressed by multiple human malignancies and has been shown to carry a highly unfavorable prognosis in patients with kidney cancer. The role of PD-L1 was evaluated as a mechanism for local stage progression in urothelial carcinoma (UC) of the bladder.METHODS. Using immunohistochemistry, PD-L1 expression was evaluated in a cohort of 280 high-risk UCs of the bladder. PD-L1 was modeled as a predictor of bladder cancer stage using ordinal logistic regression. Other covariates evaluated as potential confounders included age, gender, tumor grade, and lymphocytic infiltration. Further, PD-L1 was evaluated as a potential mechanism of bacillus Calmette-Guerin (BCG) failure in the subset of high-risk nonmuscle-invasive tumors that received this treatment.RESULTS. PD-L1 expression was observed in 7% of pTa, 16% of pT1, 23% of pT2, 30% of pT3/4, and 45% of carcinoma in situ (CIS) tumors. PD-L1 expression was associated with high-grade tumors (odds ratio [OR] = 2.4, P = .009) and tumor infiltration by mononuclear cells (OR = 5.5, P = .004). We observed that the key determinants of stage progression in this cohort were World Health Organization/International Society of Urologic Pathology (WHO/ISUP) high-grade tumor pathology (OR 4.77, 95% confidence interval [Cl]: 2.73-8.34; P < .001) and PD-L1 expression (OR = 2.20, P = .012). PD-L1 expression was found to be extremely abundant in the BCG-induced bladder granulomata in 11 of 12 patients failing BCG treatment.CONCLUSIONS. Collectively, these data indicate that tumor PD-L1 may facilitate localized stage-advancement of UC and attenuate responses to BCG immunotherapy by neutralizing T cells that normally guard against cancer invasion from the epithelium into the bladder musculature.