肿瘤相关巨噬细胞（TAMs）对肿瘤进展和化疗抗性做出贡献；因此，阐明化疗后巨噬细胞的改变功能非常重要。虽然细胞外热休克蛋白（HSP）70与治疗抗性有关，但HSP70对TAMs的影响还很少知道。在此，我们进行了体外实验和116例乳腺癌标本的免疫组化实验，以确定乳腺癌细胞在化疗后分泌的HSP70是否影响巨噬细胞功能。事实证明，表达表柿子乙素（EPI）的乳腺癌细胞与巨噬细胞的相互作用增强了肿瘤进展，而EPI促进了乳腺癌细胞分泌细胞外HSP70。使用来自HSP70沉默的乳腺癌细胞的条件培养基（CM）处理的巨噬细胞表达促肿瘤标记物CD163的表达量减少。从HSP70沉默的乳腺癌细胞的CM处理的乳腺癌细胞显示转化生长因子（TGF）-β的表达下降，当抑制TGF-β信号时，巨噬细胞的促肿瘤效应受到损害。免疫组化证明，HSP70与巨噬细胞浸润一起作为不良预后因素。因此，得出结论，化疗后细胞外HSP70水平增加，直接或间接调节乳腺癌细胞中TGF-β表达，增强TAMs的促肿瘤效应。

Tumor-associated macrophages (TAMs) contribute to tumor progression and chemoresistance; it is therefore important to clarify the altered functions of macrophages following chemotherapy. While extracellular heat shock protein (HSP) 70 is associated with therapeutic resistance, the effects of HSP70 on TAMs remain largely unknown. Here, we conducted in vitro experiments and immunohistochemistry in 116 breast carcinoma specimens to determine whether the secretion of HSP70 from breast cancer cells following chemotherapy affects macrophage function. It was revealed that the interaction of epirubicin (EPI)-exposed breast cancer cells with macrophages enhanced tumor progression, and EPI promoted the secretion of extracellular HSP70 from breast cancer cells. The expression of pro-tumorigenic macrophage marker CD163 was decreased in macrophages treated with a conditioned medium (CM) from HSP70-silenced breast cancer cells. Breast cancer cells treated with CM from HSP70-silenced breast cancer cells showed decreased expression of transforming growth factor (TGF)-β, and the pro-tumorigenic effects of macrophages were impaired when TGF-β signaling was inhibited. Immunohistochemistry demonstrated that HSP70 served as a poor prognostic factor in conjunction with macrophage infiltration. It was therefore concluded that extracellular HSP70 levels increased following chemotherapy and enhanced the pro-tumorigenic effects of TAMs, either directly or indirectly, by regulating TGF-β expression in breast cancer cells.