The immunoregulatory protein CD200 as a potentially lucrative yet elusive target for cancer therapy.
The immunoregulatory protein CD200 as a potentially lucrative yet elusive target for cancer therapy.
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免疫调节蛋白CD200是癌症治疗的潜在利润但难以捉摸的靶标。
作者：
CD200是一种免疫调节细胞表面配体，通过抑制CD200受体(CD200R)表达的抗肿瘤免疫功能而被证明具有促肿瘤作用。CD200-CD200R轴在调节免疫抑制肿瘤微环境中的这种决定性作用引起了人们对CD200作为免疫检查点抑制治疗候选靶点的越来越大的兴趣。然而，虽然CD200封闭抗体samalizumab仍处于临床测试的早期阶段，但最近出现了CD200促肿瘤作用的替代机制，这些机制超出了直接抑制抗肿瘤T细胞反应的范围，因此可能不容易被CD200抗体阻断。在这里，我们将总结目前对CD200在肿瘤微环境中的表达和功能的理解，以及在人类癌症中可能中和多种CD200机制的替代策略。
CD200 is an immunoregulatory cell surface ligand with proven pro-tumorigenic credentials via its ability to suppress CD200 receptor (CD200R)-expressing anti-tumor immune function. This definitive role for the CD200-CD200R axis in regulating an immunosuppressive tumor microenvironment has garnered increasing interest in CD200 as a candidate target for immune checkpoint inhibition therapy. However, while the CD200 blocking antibody samalizumab is still in the early stages of clinical testing, alternative mechanisms for the pro-tumorigenic role of CD200 have recently emerged that extend beyond direct suppression of anti-tumor T cell responses and, as such, may not be susceptible to CD200 antibody blockade. Herein, we will summarize the current understanding of CD200 expression and function in the tumor microenvironment as well as alternative strategies for potential neutralization of multiple CD200 mechanisms in human cancers.