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首页> 外文期刊>Cell Reports >Antibody Therapy Targeting CD47 and CD271 Effectively Suppresses Melanoma Metastasis in Patient-Derived Xenografts
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Antibody Therapy Targeting CD47 and CD271 Effectively Suppresses Melanoma Metastasis in Patient-Derived Xenografts

机译：靶向CD47和CD271的抗体疗法有效抑制了患者衍生异种移植物中的黑色素瘤转移。

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The high rate of metastasis and recurrence among melanoma patients indicates the existence of cells within melanoma that have the ability to both initiate metastatic programs and bypass immune recognition. Here, we identify CD47 as a regulator of melanoma tumor metastasis and immune evasion. Protein and gene expression analysis of clinical melanoma samples reveals that CD47, an anti-phagocytic signal, correlates with melanoma metastasis. Antibody-mediated blockade of CD47 coupled with targeting of CD271^+ melanoma cells strongly inhibits tumor metastasis in patient-derived xenografts. This therapeutic effect is mediated by drastic changes in the tumor and metastatic site immune microenvironments, both of whichwhich exhibit greatly increased density of differentiated macrophages and significantly fewer inflammatory monocytes, pro-metastatic macrophages (CCR2^+/VEGFR1^+), and neutrophils, all of which are associated with disease progression. Thus, antibody therapy that activates the innate immune response in combination with selective targeting of CD271^+ melanoma cells represents a powerful therapeutic approach against metastatic melanoma.
机译：黑色素瘤患者之间的高转移和复发率表明，黑色素瘤中存在能够启动转移程序并绕过免疫识别的细胞。在这里，我们确定CD47作为黑色素瘤肿瘤转移和免疫逃逸的调节剂。临床黑素瘤样品的蛋白质和基因表达分析表明，抗吞噬信号CD47与黑素瘤转移相关。抗体介导的CD47阻断与CD271 ^ +黑色素瘤细胞的靶向作用强烈抑制了患者来源异种移植物中的肿瘤转移。这种治疗效果是由肿瘤和转移部位免疫微环境的急剧变化介导的，它们均表现出分化巨噬细胞的密度大大提高，炎性单核细胞，促转移性巨噬细胞（CCR2 ^ + / VEGFR1 ^ +）和嗜中性白细胞显着减少，所有这些都与疾病进展有关。因此，激活先天免疫应答并选择性靶向CD271 +黑色素瘤细胞的抗体疗法代表了针对转移性黑色素瘤的有效治疗方法。

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