Tumor location determines tissue-specific recruitment of tumor-associated macrophages and antibody-dependent immunotherapy response
Tumor location determines tissue-specific recruitment of tumor-associated macrophages and antibody-dependent immunotherapy response
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DOI：
10.1126/sciimmunol.aah6413
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发表时间：
2017-01-01
影响因子：
24.8
通讯作者：
Nimmerjahn, Falk
中科院分区：
文献类型：
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作者：
Lehmann, Birgit;Biburger, Markus;Nimmerjahn, Falk
尽管最近在激活免疫细胞靶向肿瘤方面取得了进展，但一些免疫细胞（例如肿瘤相关巨噬细胞（TAM）或肿瘤相关中性粒细胞（TAN））的存在可能会促进而不是抑制肿瘤生长。然而，目前尚不清楚抗体依赖性肿瘤免疫疗法（例如细胞毒性或检查点控制抗体）如何影响不同的 TAM 或 TAN 群体，这些群体大量表达激活的 Fc γ 受体。在这项研究中，我们表明组织环境决定了哪些细胞效应途径负责抗体依赖性肿瘤免疫治疗。尽管源自 CCL2-CCR2 轴募集的 Ly6C(高) 单核细胞的 TAM 对于皮肤肿瘤的肿瘤免疫治疗至关重要，但肺肿瘤的破坏不依赖于 CCL2，并且需要集落刺激因子 2 依赖的组织驻留巨噬细胞的存在。我们的研究结果表明，TAM 可能具有双重作用，一方面促进某些组织环境中的肿瘤生长，另一方面在抗体介导的免疫治疗过程中促进肿瘤细胞的破坏。
Despite recent advances in activating immune cells to target tumors, the presence of some immune cells, such as tumor-associated macrophages (TAMs) or tumor-associated neutrophils (TANs), may promote rather than inhibit tumor growth. However, it remains unclear how antibody-dependent tumor immunotherapies, such as cytotoxic or checkpoint control antibodies, affect different TAM or TAN populations, which abundantly express activating Fc gamma receptors. In this study, we show that the tissue environment determines which cellular effector pathways are responsible for antibody-dependent tumor immunotherapy. Although TAMs derived from Ly6C(high) monocytes recruited by the CCL2-CCR2 axis were critical for tumor immunotherapy of skin tumors, the destruction of lung tumors was CCL2-independent and required the presence of colony-stimulating factor 2-dependent tissue-resident macrophages. Our findings suggest that TAMs may have a dual role not only in promoting tumor growth in certain tissue environments on the one hand but also in contributing to tumor cell destruction during antibody-mediated immunotherapy on the other hand.