Zeng Yiwei, Zhao Boyu, Yan Min, Chen Wenxin, Liu Rong, Pan Mingrui, Xie Zhen, Zhou Shuling, Liu Meijia, Fan Haonan, Wang Wenjian, Shao Nan, Kuang Xiayin, Bi Jiong
Department of Spine Surgery, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, 510063, China.
Laboratory of General Surgery, The First Affiliated Hospital, Sun Yat-Sen University, No.58 Zhongshan Rd.2, Guangzhou, 510080, Guangdong, China.
Med Oncol. 2025 Jul 25;42(9):375. doi: 10.1007/s12032-025-02914-y.
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.
新辅助化疗（NACT）在调节免疫微环境中起关键作用。然而，其对免疫检查点表达的影响以及免疫检查点在乳腺癌（BC）中的预后意义仍不清楚。在这项回顾性研究中，我们使用免疫组织化学分析来评估NACT前后BC样本中PD-L1、CD155、FGL1和半乳糖凝集素-9的表达。NACT前CD155在三阴性乳腺癌（TNBC）中的表达显著升高，并且显示出与病理完全缓解和部分缓解相关的趋势。NACT前FGL1在HER2阳性BC和TNBC中高表达。治疗后，与病理淋巴结分期较低（pN0-N1）的患者相比，病理淋巴结分期较晚（pN2-N3）的患者中更频繁地观察到较高的CD155表达。配对的治疗前和残留癌组织的比较显示，NACT后PD-L1、CD155和半乳糖凝集素-9的表达显著降低。值得注意的是，CD155表达降低与治疗反应改善显著相关，特别是在高Ki-67表达的患者中。NACT后CD155表达降低的患者比表达未改变和升高的患者具有更有利的疾病特异性生存。此外，残留BC中CD155表达降低显示出总体生存改善的趋势。治疗后PD-L1和半乳糖凝集素-9表达的变化与患者生存或病理反应无关。我们使用METABRIC数据库进行了进一步分析，发现化疗后高CD155表达与TNBC中CD8+T细胞浸润减少和预后不良相关。我们的研究结果表明，NACT诱导了BC中免疫检查点表达的显著变化。与治疗前样本相比，治疗后样本中PD-L1、CD155和半乳糖凝集素-9的表达降低。具体而言，NACT后CD155表达未改变或升高与不良的疾病特异性生存相关。此外，化疗后高CD155表达与TNBC中CD8+T细胞浸润减少和预后不良相关。
