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Specific targeting of CD163+ TAMs mobilizes inflammatory monocytes and promotes T cell-mediated tumor regression.
Journal of Experimental Medicine ( IF 12.6 ) Pub Date : 2019-10-07 , DOI: 10.1084/jem.20182124
Anders Etzerodt 1, 2 , Kyriaki Tsalkitzi 3 , Maciej Maniecki 4, 5 , William Damsky 5 , Marcello Delfini 3 , Elodie Baudoin 3 , Morgane Moulin 3, 6 , Marcus Bosenberg 5 , Jonas Heilskov Graversen 7 , Nathalie Auphan-Anezin 3 , Søren Kragh Moestrup 2, 7 , Toby Lawrence 1, 6, 8
Affiliation  

Tumor-associated macrophages (TAMs) play critical roles in tumor progression but are also capable of contributing to antitumor immunity. Recent studies have revealed an unprecedented heterogeneity among TAMs in both human cancer and experimental models. Nevertheless, we still understand little about the contribution of different TAM subsets to tumor progression. Here, we demonstrate that CD163-expressing TAMs specifically maintain immune suppression in an experimental model of melanoma that is resistant to anti–PD-1 checkpoint therapy. Specific depletion of the CD163+ macrophages results in a massive infiltration of activated T cells and tumor regression. Importantly, the infiltration of cytotoxic T cells was accompanied by the mobilization of inflammatory monocytes that significantly contributed to tumor regression. Thus, the specific targeting of CD163+ TAMs reeducates the tumor immune microenvironment and promotes both myeloid and T cell–mediated antitumor immunity, illustrating the importance of selective targeting of tumor-associated myeloid cells in a therapeutic context.



中文翻译:

CD163+ TAM 的特异性靶向动员炎症单核细胞并促进 T 细胞介导的肿瘤消退。

肿瘤相关巨噬细胞 (TAM) 在肿瘤进展中起关键作用,但也能够促进抗肿瘤免疫。最近的研究揭示了人类癌症和实验模型中 TAM 之间前所未有的异质性。尽管如此,我们仍然对不同 TAM 亚群对肿瘤进展的贡献知之甚少。在这里,我们证明了表达 CD163 的 TAM 在对抗 PD-1 检查点疗法具有抗性的黑色素瘤实验模型中特异性地维持免疫抑制。CD163 +的具体消耗巨噬细胞导致活化的 T 细胞大量浸润和肿瘤消退。重要的是,细胞毒性 T 细胞的浸润伴随着炎症单核细胞的动员,这对肿瘤消退有显着贡献。因此,CD163 + TAM的特异性靶向重新培养了肿瘤免疫微环境并促进了骨髓和 T 细胞介导的抗肿瘤免疫,说明了在治疗环境中选择性靶向肿瘤相关骨髓细胞的重要性。

更新日期:2019-10-07
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