Reprogramming Tumor-Associated Macrophages by Antibody Targeting Inhibits Cancer Progression and Metastasis
Reprogramming Tumor-Associated Macrophages by Antibody Targeting Inhibits Cancer Progression and Metastasis
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DOI：
10.1016/j.celrep.2016.04.084
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发表时间：
2016-05-31
期刊：
影响因子：
8.8
通讯作者：
Karlsson, Mikael C. I.
中科院分区：
文献类型：
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作者：
Georgoudaki, Anna-Maria;Prokopec, Kajsa E.;Karlsson, Mikael C. I.
除肿瘤细胞本身外，肿瘤还由多种细胞类型组成，包括巨噬细胞等先天免疫细胞。肿瘤相关巨噬细胞（TAM）是肿瘤微环境（TME）中存在的异质性骨髓细胞群。在这里，它们有助于免疫抑制，促进实体瘤的建立和持续存在以及转移性传播。我们发现模式识别清道夫受体 MARCO 定义了抑制性 TAM 的一种亚型，并且与临床结果相关。开发了一种抗 MARCO 单克隆抗体，它通过将 TAM 群体重编程为促炎表型并增加肿瘤免疫原性，在乳腺癌和结肠癌以及黑色素瘤模型中诱导抗肿瘤活性。这种抗肿瘤活性依赖于抑制性 Fc 受体 Fc gamma RIIB，并且还增强了检查点治疗的功效。这些结果表明，使用旨在修饰 TME 骨髓细胞的抗体进行免疫疗法代表了一种有前途的癌症治疗模式。
Tumors are composed of multiple cell types besides the tumor cells themselves, including innate immune cells such as macrophages. Tumor-associated macrophages (TAMs) are a heterogeneous population of myeloid cells present in the tumor microenvironment (TME). Here, they contribute to immunosuppression, enabling the establishment and persistence of solid tumors as well as metastatic dissemination. We have found that the pattern recognition scavenger receptor MARCO defines a subtype of suppressive TAMs and is linked to clinical outcome. An anti-MARCO monoclonal antibody was developed, which induces anti-tumor activity in breast and colon carcinoma, as well as in melanoma models through reprogramming-TAM-populations to a pro-inflammatory phenotype and increasing tumor immunogenicity. This anti-tumor activity is dependent on the inhibitory Fc-receptor, Fc gamma RIIB, and also enhances the efficacy of checkpoint therapy. These results demonstrate that immunotherapies using antibodies designed to modify myeloid cells of the TME represent a promising mode of cancer treatment.