Gynecologic oncology · 2025
Exploring novel therapeutic targets in vulvar squamous cell carcinoma.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Rhind Madeline, Abdulhaleem Khadijah, Zhu Ryan, Wei Kelly, Yi Jenny, Jamieson Amy, Horn Lars-Christian, Hoang Lien, Drew Yvette
Аннотация
OBJECTIVE: Vulvar squamous cell carcinoma (VSCC) is a rare malignancy with limited treatment options for advanced disease. This study investigates potential antibody drug conjugate (ADC) targets and explores the immune microenvironment in VSCC.
METHODS: Immunohistochemistry (IHC) was performed on tissue microarrays (TMAs) with cores from patients with VSCC to evaluate 6 potential ADC targets: Human Epidermal Growth Factor Receptor 2 (HER2), Trophoblast Cell Surface Antigen 2 (TROP2), Tissue Factor (TF), NECTIN4, Folate Receptor Alpha (FOLR1) and Claudin-18.2 (CLDN18.2). Expression of TROP2, TF and NECTIN4 was quantified using H-score. Multiplex IHC assessed immune markers (CD3+, CD8+, CD68+, PD-1/PD-L1) and combined positive scores (CPS) for programmed death-ligand 1 (PD-L1) were calculated. Clinical data was collected, including p16 and p53 status.
RESULTS: CLDN18.2 and FOLR1 were negative in all cases (n = 108) and HER2 expression was seen in only 2 cases. Intermediate to high H-score (100-300) was observed for TF in 73 % (n = 78), TROP2 in 74 % (n = 80), and NECTIN4 in 53 % (n = 57). All cases had a PD-L1 CPS ≥1 and median CPS was 66 (IQR 28-100) Exploratory analysis suggests ADC marker expression was not dependent on human papillomavirus (HPV) status. However, HPV-independent tumors appeared to have a higher infiltration of CD8+ and CD68+ cells and higher median CPS compared to HPV-associated tumors.
CONCLUSIONS: These findings are hypothesis generating and provide rationale for future clinical trials of ADCs and immune checkpoint inhibitors in VSCC. Results suggest HPV-independent tumors may be immunogenically active.
METHODS: Immunohistochemistry (IHC) was performed on tissue microarrays (TMAs) with cores from patients with VSCC to evaluate 6 potential ADC targets: Human Epidermal Growth Factor Receptor 2 (HER2), Trophoblast Cell Surface Antigen 2 (TROP2), Tissue Factor (TF), NECTIN4, Folate Receptor Alpha (FOLR1) and Claudin-18.2 (CLDN18.2). Expression of TROP2, TF and NECTIN4 was quantified using H-score. Multiplex IHC assessed immune markers (CD3+, CD8+, CD68+, PD-1/PD-L1) and combined positive scores (CPS) for programmed death-ligand 1 (PD-L1) were calculated. Clinical data was collected, including p16 and p53 status.
RESULTS: CLDN18.2 and FOLR1 were negative in all cases (n = 108) and HER2 expression was seen in only 2 cases. Intermediate to high H-score (100-300) was observed for TF in 73 % (n = 78), TROP2 in 74 % (n = 80), and NECTIN4 in 53 % (n = 57). All cases had a PD-L1 CPS ≥1 and median CPS was 66 (IQR 28-100) Exploratory analysis suggests ADC marker expression was not dependent on human papillomavirus (HPV) status. However, HPV-independent tumors appeared to have a higher infiltration of CD8+ and CD68+ cells and higher median CPS compared to HPV-associated tumors.
CONCLUSIONS: These findings are hypothesis generating and provide rationale for future clinical trials of ADCs and immune checkpoint inhibitors in VSCC. Results suggest HPV-independent tumors may be immunogenically active.
Предметные рубрики MeSH
HumansFemaleVulvar NeoplasmsCarcinoma, Squamous CellMiddle AgedCell Adhesion MoleculesBiomarkers, TumorAgedTumor MicroenvironmentImmunoconjugatesFolate Receptor 1AdultClaudinsErb-b2 Receptor Tyrosine KinasesTissue Array AnalysisImmunohistochemistryAged, 80 and overPapillomavirus InfectionsNectinsAntigens, Neoplasm