Recurrence and metastasis remain the leading cause of death in breast cancer patients due to the lack of effective treatment. A microenvironment suitable for cancer cell growth, referred to as pre-metastatic niche (PMN), is formed in distant organs before metastasis occurs. Myeloid-derived suppressor cells (MDSCs) are a heterogenous population of immature myeloid cells with immunosuppressive effects. They can expand in large numbers in breast cancer patients and participate in the formation of PMN. MDSCs can remodel the extracellular matrix of pulmonary vascular endothelial cells and recruit cancer stem cells to promote the lung metastasis of breast cancer. Furthermore, MDSCs facilitate immune evasion of breast cancer cells to impact the efficacy of immunotherapy. It is proposed that MDSCs represent a potential therapeutic target for the inhibition of recurrence and metastasis in breast cancer. Therapeutic strategies targeting MDSCs have shown promising efficacy in preclinical studies and clinical trials. This review presents a summary of the principal factors involved in the recruitment and activation of MDSCs during the formation of PMN, and outlines MDSCs functions such as immunosuppression and the current targeted therapies against MDSCs, aiming to provide new ideas for the treatment of distant metastases in breast cancer.
由于缺乏有效的治疗手段,复发转移仍然是乳腺癌患者死亡的主要原因。在转移发生之前,远处器官内已经形成了适合乳腺癌细胞生长的微环境——转移前生态位(PMN)。髓源性抑制细胞(MDSC)是一类具有免疫抑制作用的异质性未成熟髓系细胞群,可在乳腺癌患者体内大量扩增,参与PMN的形成。MDSC不仅支持乳腺癌细胞免疫逃逸,而且还可通过重塑肺血管内皮细胞外基质、招募癌症干细胞来促进乳腺癌转移的发生。此外,MDSC还能通过削弱免疫疗法的抗肿瘤效率来降低药物的治疗效果。因此,MDSC被认为是抑制乳腺癌患者复发转移的潜在治疗靶点。针对MDSC的治疗策略在临床前研究和临床试验中也显示出良好的效果。本文总结了PMN形成过程中MDSC扩增和激活的关键因素,概述了MDSC免疫抑制等功能以及目前针对MDSC的靶向免疫疗法,旨在为乳腺癌远处转移的治疗提供新思路。.
Keywords: Breast cancer; Distant metastasis; Immunosuppression; Myeloid-derived suppressor cells; Pre-metastatic niche; Review; Targeted therapy.