Dai Tiantian, Xu Zhihua, Li Yadi, Wu Mengni, Qiu Yue, Chao ZhuJun, Jiang Renhai, Chen Yan, Lu Linlin
Department of General Surgery, The First Affiliated Hospital of Soochow University, 899 Pinghai Road, Gusu District, Suzhou, 215006, Jiangsu, China.
Department of General Surgery, Baoji People's Hospital, Baoji, 721000, China.
Cancer Cell Int. 2025 Aug 4;25(1):293. doi: 10.1186/s12935-025-03932-6.
Breast cancer (BC) ranks first in morbidity and second in mortality in all female cancers, and previous studies support the contribution of tumor-associated macrophages (TAMs) to cancer progression. B7-H3 is aberrantly expressed in a variety of solid cancers, and may also promote cancer progression, but its function is still yet to be known. In this study, the importance of B7-H3 in BC pathogenesis was investigated through TAM. The expression of B7-H3 and CCR5 on macrophages/monocytes was first detected in 135 human BC tissues and peripheral blood by flow cytometry. In the tumor microenvironment, the expression of B7-H3 on TAM was positively correlated with CCR5 levels on TAM. Clinical analysis indicated that CCR5 TAM was significantly correlated with the size of tumors (T) (P = 0 .011) and E-cadherin (P < 0.0001). In vitro, knockdown of B7-H3 reduced the expression of CCL3/4 on a cell line of monocytes THP-1. Further studies showed that B7-H3 could recruit TAMs through the CCL3/4-CCR5 axis, and that CCR5TAM recruited in the tumor microenvironment could enhance BC migration and invasion. In addition, B7-H3 and CCR5 can facilitate the EMT process through the MAPK/ERK and NF-ΚB pathways. In conclusion, it is speculated that B7-H3 may regulate CCR5 TAMs through the CCL3/4-CCR5 axis, thereby promoting BC migration and invasion.
乳腺癌（BC）在所有女性癌症中发病率排名第一，死亡率排名第二，先前的研究支持肿瘤相关巨噬细胞（TAM）对癌症进展的作用。B7-H3在多种实体癌中异常表达，也可能促进癌症进展，但其功能尚不清楚。在本研究中，通过TAM研究了B7-H3在BC发病机制中的重要性。首先通过流式细胞术检测了135例人类BC组织和外周血中巨噬细胞/单核细胞上B7-H3和CCR5的表达。在肿瘤微环境中，TAM上B7-H3的表达与TAM上CCR5水平呈正相关。临床分析表明，CCR5 TAM与肿瘤大小（T）（P = 0.011）和E-钙黏蛋白（P < 0.0001）显著相关。在体外，敲低B7-H3可降低单核细胞THP-1细胞系上CCL3/4的表达。进一步研究表明，B7-H3可通过CCL3/4-CCR5轴招募TAM，肿瘤微环境中招募的CCR5TAM可增强BC的迁移和侵袭。此外，B7-H3和CCR5可通过MAPK/ERK和NF-κB途径促进EMT过程。总之，推测B7-H3可能通过CCL3/4-CCR5轴调节CCR5 TAM，从而促进BC的迁移和侵袭。
