Breast Tumor Immunology Laboratory, Dana-Farber Cancer Institute, Boston, MA, United States.
Division of Breast Surgery, Department of Surgery, Brigham and Women's Hospital, Boston, MA, United States.
Front Immunol. 2021 Apr 23;12:643771. doi: 10.3389/fimmu.2021.643771. eCollection 2021.
Macrophages are crucial innate immune cells that maintain tissue homeostasis and defend against pathogens; however, their infiltration into tumors has been associated with adverse outcomes. Tumor-associated macrophages (TAMs) represent a significant component of the inflammatory infiltrate in breast tumors, and extensive infiltration of TAMs has been linked to poor prognosis in breast cancer. Here, we detail how TAMs impede a productive tumor immunity cycle by limiting antigen presentation and reducing activation of cytotoxic T lymphocytes (CTLs) while simultaneously supporting tumor cell survival, angiogenesis, and metastasis. There is an urgent need to overcome TAM-mediated immune suppression for durable anti-tumor immunity in breast cancer. To date, failure to fully characterize TAM biology and classify multiple subsets has hindered advancement in therapeutic targeting. In this regard, the complexity of TAMs has recently taken center stage owing to their subset diversity and tightly regulated molecular and metabolic phenotypes. In this review, we reveal major gaps in our knowledge of the functional and phenotypic characterization of TAM subsets associated with breast cancer, before and after treatment. Future work to characterize TAM subsets, location, and crosstalk with neighboring cells will be critical to counteract TAM pro-tumor functions and to identify novel TAM-modulating strategies and combinations that are likely to enhance current therapies and overcome chemo- and immuno-therapy resistance.
巨噬细胞是维持组织内稳态和抵御病原体的重要先天免疫细胞；然而，它们浸润肿瘤与不良预后相关。肿瘤相关巨噬细胞（TAMs）是乳腺癌炎症浸润的重要组成部分，TAMs 的广泛浸润与乳腺癌预后不良相关。在这里，我们详细介绍了 TAMs 如何通过限制抗原呈递和减少细胞毒性 T 淋巴细胞（CTL）的激活，同时支持肿瘤细胞存活、血管生成和转移，来阻碍有效的肿瘤免疫循环。为了在乳腺癌中获得持久的抗肿瘤免疫，迫切需要克服 TAM 介导的免疫抑制。迄今为止，由于未能充分表征 TAM 生物学并对多个亚群进行分类，因此在治疗靶向方面进展缓慢。在这方面，由于 TAMs 亚群多样性和严格调控的分子和代谢表型，其复杂性最近成为关注焦点。在这篇综述中，我们揭示了与乳腺癌治疗前后 TAM 亚群功能和表型特征相关的主要知识空白。未来对 TAM 亚群的特征、位置以及与邻近细胞的相互作用进行研究，对于抵抗 TAM 促进肿瘤的功能以及鉴定新的 TAM 调节策略和组合以增强现有治疗方法并克服化疗和免疫治疗耐药性将是至关重要的。
