巨噬细胞：治疗抵抗定义的肿瘤微环境中的关键协调者。
Macrophages: Key orchestrators of a tumor microenvironment defined by therapeutic resistance.
机构信息
Department of Biology, Mansfield University, Mansfield, PA 16933, USA.
Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA 19104, USA; Division of Hematology-Oncology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
出版信息
Mol Immunol. 2019 Jun;110:3-12. doi: 10.1016/j.molimm.2017.12.003. Epub 2017 Dec 19.
Macrophages have emerged as promising therapeutic targets in cancer. Within tumor tissue, macrophages foster tumor development, invasion, and metastasis. As the phenotype of macrophages is inherently pliable and dependent on cues received from the surrounding microenvironment, macrophages co-evolve with malignant and other non-malignant cells during cancer progression. In doing so, they establish a microenvironment that is therapeutically resistant and thwarts the productivity of T cell immunosuveillance. Strategies designed to deplete, inhibit, or redirect macrophages with anti-tumor activity are being explored to reverse the pro-tumor properties of macrophages that are commonly observed in cancer. In this review, we discuss our current understanding of the mechanisms that regulate macrophage recruitment to tumors, their impact on the tumor microenvironment, and their promise as therapeutic targets for improving the efficacy of cytotoxic- and immune-based therapies.
巨噬细胞已成为癌症治疗的有前途的靶点。在肿瘤组织中，巨噬细胞促进肿瘤的发展、侵袭和转移。由于巨噬细胞的表型本质上是灵活的，并取决于周围微环境中接收到的线索，因此在癌症进展过程中，巨噬细胞与恶性和其他非恶性细胞共同进化。这样，它们建立了一个治疗上具有抗性的微环境，并破坏了 T 细胞免疫监视的有效性。目前正在探索旨在耗尽、抑制或重定向具有抗肿瘤活性的巨噬细胞的策略，以逆转在癌症中常见的巨噬细胞的促肿瘤特性。在这篇综述中，我们讨论了我们对调节巨噬细胞向肿瘤募集的机制、它们对肿瘤微环境的影响以及它们作为提高细胞毒性和免疫治疗疗效的治疗靶点的潜力的现有理解。
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