Trop-2 expression and the tumor immune microenvironment in cervical cancer.

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. 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. 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. 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. Copyright © 2024 Elsevier Inc. All rights reserved.

Citation

Yohei Chiba, Yuki Kojima, Shu Yazaki, Hiroshi Yoshida, Shigemasa Takamizawa, Rui Kitadai, Ayumi Saito, Hitomi Sumiyoshi Okuma, Tadaaki Nishikawa, Tatsunori Shimoi, Kazuki Sudo, Emi Noguchi, Masaya Uno, Mitsuya Ishikawa, Tomoyasu Kato, Yasuhiro Fujiwara, Kan Yonemori. Trop-2 expression and the tumor immune microenvironment in cervical cancer. Gynecologic oncology. 2024 Aug;187:51-57

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PMID: 38723340

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