Specific targeting of CD163+ TAMs mobilizes inflammatory monocytes and promotes T cell-mediated tumor regression
Specific targeting of CD163+ TAMs mobilizes inflammatory monocytes and promotes T cell-mediated tumor regression
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DOI：
10.1084/jem.20182124
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发表时间：
2019-10-01
影响因子：
15.3
通讯作者：
Lawrence, Toby
中科院分区：
文献类型：
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作者：
Etzerodt, Anders;TsaLkitzi, Kyriaki;Lawrence, Toby
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。最近的研究表明，在人类癌症和实验模型中，TAM之间存在前所未有的异质性。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CD 163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。CD 163（+）巨噬细胞的特异性耗竭导致活化T细胞的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性单核细胞的动员，这显著有助于肿瘤消退。因此，CD 163（+）TAM的特异性靶向重新教育肿瘤免疫微环境，并促进骨髓和T细胞介导的抗肿瘤免疫，说明在治疗背景下选择性靶向肿瘤相关骨髓细胞的重要性。
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.