Profiling Fibroblast Growth Factor Receptor 3 Expression Based on the Immune Microenvironment in Upper Tract Urothelial Carcinoma.

IF 8.3 1区 医学 Q1 ONCOLOGY European urology oncology Pub Date : 2024-12-01 Epub Date: 2024-02-05 DOI:10.1016/j.euo.2024.01.013
Keisuke Shigeta, Kazuhiro Matsumoto, Sotaro Kitaoka, Minami Omura, Kota Umeda, Yuki Arita, Shuji Mikami, Keishiro Fukumoto, Yota Yasumizu, Nobuyuki Tanaka, Toshikazu Takeda, Shinya Morita, Takeo Kosaka, Ryuichi Mizuno, Satoshi Hara, Mototsugu Oya
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Abstract

Background: Although several studies have shown favorable outcomes in upper tract urothelial carcinoma (UTUC) with fibroblast growth factor receptor 3 (FGFR3) mutations and/or expression, the relationship between immune cell markers and FGFR3 expression remains unknown.

Objective: To clarify the FGFR3-based immune microenvironment and investigate biomarkers to predict the treatment response to pembrolizumab (Pem) in patients with UTUC.

Design, setting, and participants: We conducted immunohistochemical staining in 214 patients with UTUC. The expression levels of FGFR3, CD4, CD8, CD68, CD163, CD204, and programmed cell death ligand 1 (PD-L1) were examined.

Intervention: All UTUC patients underwent radical nephroureterectomy.

Outcome measurements and statistical analysis: We assessed the relationship between these immune markers and patient prognosis.

Results and limitations: A total of 109 (50.9%) patients showed high FGFR3 expressions and a favorable prognosis compared with the remaining patients. Among the six immune markers, CD8 high expression was an independent favorable factor, whereas CD204 expression was an independent prognostic factor for cancer death. From the FGFR3-based immune clustering, three immune clusters were identified. Cluster A showed low FGFR3 with tumor-associated macrophage-rich components (CD204+) followed by a poor prognosis due to a poor response to Pem. Cluster B showed low FGFR3 with an immune hot component (CD8+), followed by the most favorable prognosis owing to a good response to Pem. Cluster C showed high FGFR3 expression but an immune cold component, followed by a favorable prognosis due to the high FGFR3 expression, but a poor response was confirmed with Pem.

Conclusions: Although most patients exhibit a poor response to Pem, individuals with low FGFR3 expression and immune hot status may benefit clinically from Pem treatment.

Patient summary: We conducted immunohistochemical staining to evaluate fibroblast growth factor receptor 3 (FGFR3)-related immune microenvironment by evaluating the expressions of CD4, CD8, CD68, CD163, CD204, and PD-L1 in 214 upper tract urothelial carcinoma patients. We identified three distinct immune clusters based on FGFR3 expressions and found that patients with a low FGFR3 expression but immune hot status received the maximum benefit from an immune checkpoint inhibitor.

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基于上尿路上皮癌免疫微环境的成纤维细胞生长因子受体 3 表达谱分析
背景:尽管多项研究显示,成纤维细胞生长因子受体3(FGFR3)突变和/或表达的上尿路尿路上皮癌(UTUC)具有良好的预后,但免疫细胞标志物与FGFR3表达之间的关系仍然未知:明确基于FGFR3的免疫微环境,研究预测UTUC患者对pembrolizumab(Pem)治疗反应的生物标志物:我们对214名UTUC患者进行了免疫组化染色。对FGFR3、CD4、CD8、CD68、CD163、CD204和程序性细胞死亡配体1(PD-L1)的表达水平进行了检测:所有UTUC患者均接受根治性肾切除术:我们评估了这些免疫标记物与患者预后之间的关系:共有109例(50.9%)患者表现为FGFR3高表达,与其余患者相比预后良好。在六种免疫标记物中,CD8高表达是一个独立的有利因素,而CD204表达则是癌症死亡的独立预后因素。根据基于 FGFR3 的免疫聚类,确定了三个免疫聚类。群组A显示低FGFR3和肿瘤相关的富含巨噬细胞的成分(CD204+),随后由于对Pem反应不佳,预后较差。群组 B 显示低 FGFR3 和免疫热成分(CD8+),由于对 Pem 反应良好,预后最有利。C组显示 FGFR3 高表达,但有免疫冷成分,由于 FGFR3 高表达,预后较好,但对 Pem 的反应较差:患者摘要:我们对214例上消化道尿路上皮癌患者进行了免疫组化染色,通过评估CD4、CD8、CD68、CD163、CD204和PD-L1的表达来评价成纤维细胞生长因子受体3(FGFR3)相关的免疫微环境。我们根据表皮生长因子受体3的表达确定了三个不同的免疫集群,并发现表皮生长因子受体3表达较低但处于免疫热状态的患者从免疫检查点抑制剂中获益最大。
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来源期刊
CiteScore
15.50
自引率
2.40%
发文量
128
审稿时长
20 days
期刊介绍: Journal Name: European Urology Oncology Affiliation: Official Journal of the European Association of Urology Focus: First official publication of the EAU fully devoted to the study of genitourinary malignancies Aims to deliver high-quality research Content: Includes original articles, opinion piece editorials, and invited reviews Covers clinical, basic, and translational research Publication Frequency: Six times a year in electronic format
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