Zhang Qi, Liu Xiaodi, Wei Qiuxia, Xiong Shiyu, Luo Wanrong, Zhou Yingshi, Cao Jincheng, Xu Xiaolin, Liu Rongbin, Tang Xinyu, Zhang Wenyue, Luo Baoming
Department of Ultrasound, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510120, China; Guangdong Provincial Key Laboratory of Malignant Tumour Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510120, China; Department of Ultrasound, The First Affiliated Hospital with Nanjing Medical University, Nanjing, 210029, China.
Department of Ultrasound, Laboratory of Ultrasound Imaging and Drug, West China Hospital, Sichuan University, Chengdu, 610041, China.
Redox Biol. 2025 Mar;80:103485. doi: 10.1016/j.redox.2024.103485. Epub 2024 Dec 28.
Chemotherapy is important in the systemic therapy for breast cancer. However, after chemotherapy, the left living tumour cells are more progressive. There is an urgent need to study the underlying mechanism which is still unclear to further improve the therapeutic efficacy of chemotherapy in breast cancer. Here we find a pro-tumour effect of the apoptotic cells induced by the chemotherapy, which is mediated by a new subset of macrophages undergoing LC3-associated phagocytosis (LAP). By transferring exosomal S100A11 into the living tumour cells after chemotherapy, the macrophage exhibits a more pro-tumour phenotype than classic M2-type macrophages. Moreover, S100A11 binds to IFITM3, inducing Akt phosphorylation of living tumour cells after chemotherapy, which promotes tumour progression. Of note, Akt inhibitor can enhance the therapeutic effcicay of chemotherapy in breast cancer. This study provides a novel mechanistic link between tumour-associated macrophages and breast cancer, uncovering Akt as a potential therapeutic target to improve chemotherapy efficacy.
化疗在乳腺癌的全身治疗中至关重要。然而，化疗后残留的存活肿瘤细胞更具侵袭性。迫切需要研究其潜在机制（目前仍不清楚），以进一步提高乳腺癌化疗的疗效。在此，我们发现化疗诱导的凋亡细胞具有促肿瘤作用，这是由经历LC3相关吞噬作用（LAP）的新亚群巨噬细胞介导的。化疗后，通过将外泌体S100A11转移至存活肿瘤细胞中，巨噬细胞表现出比经典M2型巨噬细胞更强的促肿瘤表型。此外，S100A11与IFITM3结合，诱导化疗后存活肿瘤细胞的Akt磷酸化，从而促进肿瘤进展。值得注意的是，Akt抑制剂可增强乳腺癌化疗的疗效。本研究揭示了肿瘤相关巨噬细胞与乳腺癌之间的新型机制联系，发现Akt是提高化疗疗效的潜在治疗靶点。
