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宫颈癌中 Trop-2 表达与肿瘤免疫微环境

英文原题:Trop-2 expression and the tumor immune microenvironment in cervical cancer.

PubMed 2024/05/08(内容时间) Gynecol Oncol Q1 · IF 4.5(JCR 2025)

研究概要

宫颈癌中Trop-2的表达与瘤内TILs水平升高相关,提示Trop-2靶向治疗单独或联合免疫检查点抑制剂具有潜在应用价值。

研究思路结论见上方概要

滋养层细胞表面抗原2(Trop-2)是一种跨膜糖蛋白,在多种癌症中过表达,作为肿瘤反应性T细胞的靶点具有免疫学意义。我们旨在研究宫颈癌中Trop-2表达与肿瘤免疫微环境之间的关联。

本研究纳入2000年至2020年间在我院接受初次手术的123例宫颈癌患者。使用抗Trop-2单克隆抗体克隆MAB650评估Trop-2表达。同时评估免疫生物标志物,包括PD-L1(22C3)、CD3(PS1)和CD8(4B11)。Trop-2和PD-L1阳性分别定义为H-score ≥ 10和联合阳性评分(CPS)≥1。在五个选定的独立区域评估TIL(肿瘤浸润淋巴细胞)(TILs)。分析Trop-2表达与免疫生物标志物之间的相关性。

该队列包括鳞状细胞癌(SCC)患者(54.5%)和非SCC患者(45.5%)。Trop-2在84.6%的样本中呈阳性,且在SCC中更常见(SCC vs. 非SCC;97.0% vs. 69.6%,p < 0.001)。瘤内CD3+和CD8+ TIL在Trop-2阳性病例中显著更常见(CD3,Mann-Whitney U = 383,p < 0.0001;CD8,U = 442,p < 0.0001)。此外,Trop-2 H-score与免疫标志物之间发现显著正相关(CD3+ TIL,r = 0.295,p < 0.001;CD8+ TIL,r = 0.267,p = 0.001;PD-L1 CPS,r = 0.178,p = 0.025)。未检测到TIL与其他临床病理特征(包括预后)之间的显著关联。

展开英文摘要原文

OBJECTIVE: Trophoblast Cell Surface Antigen 2 (Trop-2) is a transmembrane glycoprotein that is overexpressed in various cancers, with immunological significance as a target for tumor-reactive T-cells. We aimed to investigate the association between the expression of Trop-2 and the tumor immune microenvironment in cervical cancer. METHODS: The study included 123 patients with cervical cancer who underwent primary surgery between 2000 and 2020 in our hospital. Trop-2 expression was evaluated using anti-Trop-2 monoclonal antibody clone MAB650. Immune biomarkers, including PD-L1 (22C3), CD3 (PS1), and CD8 (4B11), were also evaluated. Trop-2 and PD-L1 positivity were defined by an H-score ≥ 10 and a combined positive score (CPS) ≥1, respectively. Tumor-infiltrating lymphocytes (TILs) were assessed in the five selected independent areas. The correlation between Trop-2 expression and immune biomarkers was analyzed. RESULTS: The cohort comprised patients with squamous cell carcinoma (SCC) (54.5%) and non-SCC (45.5%). Trop-2 was positive in 84.6% of samples and more commonly expressed in SCC (SCC vs. non-SCC; 97.0% vs. 69.6%, p < 0.001). Intratumoral CD3+ and CD8 + TILs were significantly more common in Trop-2-positive cases (CD3, Mann-Whitney U = 383, p < 0.0001; CD8, U = 442, p < 0.0001). Additionally, significant positive correlations were found between the Trop-2 H-score and immune markers (CD3 + TILs, r = 0.295, p < 0.001; CD8 + TILs, r = 0.267, p = 0.001; PD-L1 CPS, r = 0.178, p = 0.025). No significant associations were detected between TILs and other clinicopathological features, including prognosis. CONCLUSION: Expression of Trop-2 in cervical cancer is associated with increased levels of intratumoral TILs, indicating the potential of Trop-2 targeted therapy alone or in combination with immune checkpoint inhibitors.

论文信息

作者
Chiba Y、Kojima Y、Yazaki S、Yoshida H、Takamizawa S、Kitadai R、Saito A、Okuma HS
第一作者单位
Department of Medical Oncology, National Cancer Center Hospital, Tokyo, Japan. Electronic address: ychiba@ncc.go.jp.Japan
通讯作者单位
Department of Medical Oncology, National Cancer Center Hospital, Tokyo, Japan. Electronic address: kyonemor@ncc.go.jp.Japan
期刊
Gynecologic oncology2024 Aug
原文标识
PubMed 38723340 · DOI 10.1016/j.ygyno.2024.04.022