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首页> 外文期刊>EBioMedicine >Targeting CD147 for T to NK Lineage Reprogramming and Tumor Therapy
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Targeting CD147 for T to NK Lineage Reprogramming and Tumor Therapy

机译：将CD147靶向用于T到NK谱系重编程和肿瘤治疗

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CD147 is highly expressed on the surface of numerous tumor cells to promote invasion and metastasis. Targeting these cells with CD147-specific antibodies has been validated as an effective approach for lung and liver cancer therapy. In the immune system, CD147 is recognized as a co-stimulatory receptor and impacts the outcome of thymic selection. Using T cell-specific deletion, we showed here that in thymus CD147 is indispensable for the stable @a@b T cell lineage commitment: loss of CD147 biases both multipotent DN (double negative) and fully committed DP (double positive) cells into innate NK-like lineages. Mechanistically, CD147 deficiency results in impaired Wnt signaling and expression of BCL11b, a master transcription factor in determining T cell identity. In addition, functional blocking of CD147 by antibody phenocopies genetic deletion to enrich NK-like cells in the periphery. Furthermore, using a melanoma model and orthotopic liver cancer transplants, we showed that the augmentation of NK-like cells strongly associates with resistance against tumor growth upon CD147 suppression. Therefore, besides its original function in tumorigenesis, CD147 is also an effective surface target for immune modulation in tumor therapy.
机译：CD147在许多肿瘤细胞的表面高度表达，以促进侵袭和转移。用CD147特异性抗体靶向这些细胞已被证实是肺癌和肝癌治疗的有效方法。在免疫系统中，CD147被认为是一种共刺激受体，会影响胸腺选择的结果。使用T细胞特异性缺失，我们在这里显示了在胸腺中CD147对于稳定的@ a @ b T细胞谱系承诺是必不可少的：CD147的丢失会使多能性DN（双阴性）和完全定型的DP（双阳性）细胞偏向先天NK样谱系。从机理上讲，CD147缺乏导致Wnt信号传导和BCL11b的表达受损，BCL11b是确定T细胞身份的主要转录因子。另外，通过抗体表型遗传删除功能性阻断CD147，以富集周围的NK样细胞。此外，使用黑色素瘤模型和原位肝癌移植，我们显示NK样细胞的增加与CD147抑制后对肿瘤生长的抗性密切相关。因此，除了其在肿瘤发生中的原始功能外，CD147还是肿瘤治疗中免疫调节的有效表面靶标。

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