Department of Radiation Oncology, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Cell Rep. 2022 Jun 21;39(12):110977. doi: 10.1016/j.celrep.2022.110977.
The standard of care is unsuccessful to treat recurrent and aggressive soft-tissue sarcomas. Interventions aimed at targeting components of the tumor microenvironment have shown promise for many solid tumors yet have been only marginally tested for sarcoma, partly because knowledge of the sarcoma microenvironment composition is limited. We employ single-cell RNA sequencing to characterize the immune composition of an undifferentiated pleiomorphic sarcoma mouse model, showing that macrophages in the sarcoma mass exhibit distinct activation states. Sarcoma cells use the pleiotropic cytokine macrophage migration inhibitory factor (MIF) to interact with macrophages expressing the CD74 receptor to switch macrophages' activation state and pro-tumorigenic potential. Blocking the expression of MIF in sarcoma cells favors the accumulation of macrophages with inflammatory and antigen-presenting profiles, hence reducing tumor growth. These data may pave the way for testing new therapies aimed at re-shaping the sarcoma microenvironment, in combination with the standard of care.
标准治疗方案对于复发性和侵袭性软组织肉瘤的疗效并不理想。针对肿瘤微环境成分的干预措施已在许多实体瘤中显示出前景，但在肉瘤方面的测试却微乎其微，部分原因是对肉瘤微环境成分的了解有限。我们采用单细胞 RNA 测序来描述未分化多形性肉瘤小鼠模型的免疫组成，结果表明肉瘤块中的巨噬细胞表现出不同的激活状态。肉瘤细胞利用多效细胞因子巨噬细胞移动抑制因子 (MIF) 与表达 CD74 受体的巨噬细胞相互作用，改变巨噬细胞的激活状态和促肿瘤潜能。阻断肉瘤细胞中 MIF 的表达有利于积累具有炎症和抗原呈递特征的巨噬细胞，从而减少肿瘤生长。这些数据可能为测试旨在重塑肉瘤微环境的新疗法铺平道路，与标准治疗相结合。
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