Tumor immune microenvironment in non-muscle-invasive urothelial carcinoma of the bladder
Tumor immune microenvironment in non-muscle-invasive urothelial carcinoma of the bladder
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DOI：
10.1016/j.humpath.2019.04.003
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发表时间：
2019-07-01
期刊：
影响因子：
3.3
通讯作者：
Netto, George J.
中科院分区：
文献类型：
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作者：
Eich, Marie-Lisa;Chaux, Alcides;Netto, George J.
免疫治疗已在包括晚期尿路上皮癌在内的多种肿瘤类型中发挥重要作用。几十年来，非侵袭性尿路上皮病变一直被用卡介苗(BCG)膀胱内注射治疗。考虑到这些肿瘤的一部分治疗失败，正在进行的临床试验正在积极地研究检查点抑制剂在这组患者中的作用。本研究旨在描述通过连续活检获得的非肌肉浸润性尿路上皮癌标本中PD-L1、CD8和FOXP3在肿瘤微环境中的表达，并评估其在预测疾病预后方面的潜在作用。肿瘤细胞中>；1%和>；5%PD-L1表达的患者与PD-L1表达较低的患者相比，在随后的任何一次活检中复发的相对风险(RR)较低(RR分别为0.83[P=.009]和0.81[P=.03])。FOXP3在瘤周淋巴细胞中高表达的患者在任何一次活检中肿瘤分级进展的风险都较低(RR，0.2；P=0.02)。瘤内淋巴细胞FOXP3/CD8表达比值为>；1的肿瘤分级风险较低(RR，0.28；P=0.04)。卡介苗治疗后FOXP3、CD8和PD-L1阳性淋巴细胞数虽较治疗前增加，但差异无统计学意义。在未接受卡介苗治疗的患者中，肿瘤细胞和瘤周淋巴细胞中PD-L1的表达在系列活组织检查中有所不同，这表明需要额外的方法来评估非肌肉浸润性尿路上皮癌患者接受免疫治疗的资格。(C)2019 Elsevier Inc.保留所有权利。
Immunotherapy has gained significance in a variety of tumor types including advanced urothelial carcinoma. Noninvasive urothelial lesions have been treated with intravesical Bacillus-Calmette-Guerin (BCG) for decades. Given treatment failure in a subset of these tumors, ongoing clinical trials investigating the role of checkpoint inhibitors are actively pursued in this group of patients. The present study aims to delineate PD-L1, CD8, and FOXP3 expression in tumor microenvironment in non-muscle-invasive urothelial carcinoma samples obtained via sequential biopsies and to assess its potential role in predicting disease outcome. Cases with >1% and> 5% PD-L1 expression in tumor cells showed lower relative risk (RR) to recur at any subsequent biopsy compared with those with lower PD-L1 expression (RRs, 0.83 [P = .009] and 0.81 [P = .03], respectively). Cases with higher expression of FOXP3 in peritumoral lymphocytes were at lower risk for tumor grade progression at any biopsy (RR, 0.2; P = .02). Tumors with FOXP3/CD8 expression ratio of >1 in intratumoral lymphocytes had lower risk of grade progression (RR, 0.28; P = .04). Although higher number of FOXP3-, CD8-, and PD-L1-positive lymphocytes were encountered after BCG treatment, the findings did not reach statistical significance. In patients without BCG treatment, PD-L1 expression in tumor cells and peritumoral lymphocytes varied across serial biopsies, suggesting the need for additional approaches to assess eligibility for immunotherapy in non-muscle-invasive urothelial carcinoma patients. (C) 2019 Elsevier Inc. All rights reserved.