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. 2024 Aug:187:51-57.
doi: 10.1016/j.ygyno.2024.04.022. Epub 2024 May 8.

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

Yohei Chiba  1 , Yuki Kojima  2 , Shu Yazaki  3 , Hiroshi Yoshida  4 , Shigemasa Takamizawa  5 , Rui Kitadai  6 , Ayumi Saito  7 , Hitomi Sumiyoshi Okuma  8 , Tadaaki Nishikawa  9 , Tatsunori Shimoi  10 , Kazuki Sudo  11 , Emi Noguchi  12 , Masaya Uno  13 , Mitsuya Ishikawa  14 , Tomoyasu Kato  15 , Yasuhiro Fujiwara  16 , Kan Yonemori  17
Affiliations

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

Yohei Chiba et al. Gynecol Oncol. 2024 Aug.

Abstract

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.

Keywords: Cervical cancer; PD-L1; Trophoblast cell surface antigen 2; Tumor-infiltrating lymphocytes.

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Conflict of interest statement

Declaration of competing interest Yohei Chiba, Yuki Kojima, Shu Yazaki, Hiroshi Yoshida, Shigemasa Takamizawa, Rui Kitadai, Ayumi Saito, Hitomi Sumiyoshi-Okuma, Tatsunori Shimoi, Kazuki Sudo, Masaya Uno, Mitsuya Ishikawa, and Tomoyasu Kato have nothing to disclose. Tadaaki Nishikawa reports personal fees from Takeda Pharmaceutical Company, Eisai, and AstraZeneca outside of the submitted work. Emi Noguchi reports personal fees from Pfizer, Taiho, Eli Lilly, AstraZeneca, Chugai, and Eisai outside the submitted work. Yasuhiro Fujiwara reports personal fees from AstraZeneca, Chugai, Daiichi Sankyo, Bristol-Myers, SRL, and Santen outside the submitted work. Kan Yonemori reports personal fees from Pfizer, AstraZeneca, Eisai, Takeda Pharmaceutical Company, Chugai, Ono Pharmaceutical Company, Novartis, and Daiichi Sankyo outside the submitted work.

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