Exploring novel therapeutic targets in vulvar squamous cell carcinoma

Area of Science:

• Oncology
• Immunology
• Drug Development

Background:

• Vulvar squamous cell carcinoma (VSCC) is a rare cancer with limited advanced treatment options.
• Antibody drug conjugates (ADCs) offer a targeted therapy approach.
• Understanding the tumor immune microenvironment is crucial for developing immunotherapies.

Purpose of the Study:

• To identify potential antibody drug conjugate (ADC) targets in VSCC.
• To analyze the immune microenvironment, including immune cell infiltration and PD-L1 expression.
• To explore correlations between ADC targets, immune markers, and human papillomavirus (HPV) status.

Main Methods:

• Immunohistochemistry (IHC) was used to assess the expression of six potential ADC targets (HER2, TROP2, TF, NECTIN4, FOLR1, CLDN18.2) in 108 VSCC patient samples.
• Expression levels of TROP2, TF, and NECTIN4 were quantified using H-score.
• Multiplex IHC evaluated immune markers (CD3+, CD8+, CD68+, PD-1/PD-L1), and programmed death-ligand 1 (PD-L1) combined positive scores (CPS) were calculated.

Main Results:

• TROP2 (74%), TF (73%), and NECTIN4 (53%) showed intermediate to high expression, indicating potential ADC targets.
• CLDN18.2 and FOLR1 were negative, and HER2 expression was minimal.
• All cases exhibited PD-L1 expression (CPS ≥1), with a median CPS of 66. HPV-independent tumors demonstrated higher CD8+ and CD68+ cell infiltration and higher median PD-L1 CPS compared to HPV-associated tumors.

Conclusions:

• TROP2, TF, and NECTIN4 are promising targets for ADCs in VSCC.
• The study provides a rationale for clinical trials combining ADCs and immune checkpoint inhibitors in VSCC.
• HPV-independent VSCC tumors appear to be more immunologically active, suggesting a potential benefit from immunotherapy.