Trop2, Nectin-4, and PD-L1 expression profiles in esophageal squamous cell carcinoma: Implications for combined immunotherapy and ADC targeted therapies.

Aim: Trop2, Nectin-4, and PD-L1 are targets of antibody-drug conjugate (ADC) drugs and immunological agents, respectively, closely related to the biological characteristics of malignant tumors. This study analyzed the expression and clinical significance of Trop2, Nectin-4, and PD-L1 and their association with esophageal squamous cell carcinoma (ESCC).

Methods: Clinicopathological data of 140 patients with ESCC undergoing radical resection at the Affiliated Hospital of Qingdao University were retrospectively collected. Immunohistochemistry (IHC) was conducted to assess the expression of Trop2, Nectin-4, and PD-L1 in the specimens, with quantification and categorization of expression levels by the histochemistry score (H-score). For PD-L1, the combined positive score (CPS) was also evaluated.

Results: Positivity rates for Trop2, Nectin-4, and PD-L1 were 99.3 %, 95.7 %, and 43.6 %, respectively. Trop2 correlated with lymphatic vessel invasion, lymph node invasion, and advanced tumor stage, while Nectin-4 was associated with lymphatic vessel invasion, peripheral nerve invasion, lymph node invasion, and advanced pathological T stage. Additionally, PD-L1-positive patients exhibited higher rates of elevated Trop2 and Nectin-4 expression, increased lymphatic vessel invasion, and advanced pathological T stage compared to PD-L1-negative patients. Furthermore, among individuals potentially eligible for immunotherapy (PD-L1 CPS >10), PD-L1 expression displayed a significantly weak correlation with Nectin-4 expression. Furthermore, Trop2 served as an independent poor prognostic indicator for ESCC patients.

Conclusions: The expression landscape of Trop2, Nectin-4, and PD-L1 in ESCC indicated the feasibility of combining immunotherapy with ADC drug-targeted therapies.