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
目的
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。
方法
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。
结果
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