Expression and clinical significance of CD155, FGL1, Galectin-9, and PD‑L1 in breast cancer with neoadjuvant chemotherapy.

Abstract

Neoadjuvant chemotherapy (NACT) plays a pivotal role in modulating the immune microenvironment. However, its impact on immune checkpoint expression and the prognostic significance of immune checkpoints in breast cancer (BC) remain unclear. In this retrospective study, we used immunohistochemistry assays to evaluate PD-L1, CD155, FGL1, and Galectin-9 expression in pre- and post-NACT BC samples. CD155 expression before NACT was significantly elevated in triple-negative breast cancer (TNBC) and showed a tendency to be associated with pathological complete and partial responses. FGL1 was highly expressed in HER2-positive BC and TNBC before NACT. After treatment, higher CD155 expression was more frequently observed in patients with advanced pathological lymph node stages (pN2-N3) than in those with lower stages (pN0-N1). Comparison of paired pre-treatment and residual cancer tissues revealed a significant decrease in PD-L1, CD155, and Galectin-9 expression following NACT. Notably, decreased CD155 expression significantly correlated with improved therapeutic response, particularly in patients with high Ki-67 expression. Patients with reduced CD155 expression after NACT had more favourable disease-specific survival than those with unchanged and increased expression. Moreover, decreased CD155 expression in residual BC showed a trend toward improved overall survival. Changes in PD-L1 and Galectin-9 expression after therapy were not associated with patient survival or pathological response. We conducted further analysis using the METABRIC database and found high CD155 expression after chemotherapy was related to decreased CD8+ T cell infiltration and poor outcome in TNBC. Our findings indicated that NACT induced significant changes in immune checkpoint expression in BC. PD-L1, CD155, and Galectin-9 expression were reduced in post-treatment samples compared to pre-treatment samples. Specifically, unchanged or elevated CD155 expression after NACT was associated with poor disease-specific survival. Further more, high CD155 expression after chemotherapy was related to decreased CD8+ T cell infiltration and poor outcome in TNBC.