Crucial role of CD69 in anti-tumor immunity through regulating the exhaustion of tumor-infiltrating T cells
Crucial role of CD69 in anti-tumor immunity through regulating the exhaustion of tumor-infiltrating T cells
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DOI：
10.1093/intimm/dxy050
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发表时间：
2018-12-01
影响因子：
4.4
通讯作者：
Nakayama, Toshinori
中科院分区：
文献类型：
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作者：
Mita, Yukiyoshi;Kimura, Motoko Y.;Nakayama, Toshinori
在癌症治疗中引入免疫检查点抑制剂突出了抗肿瘤免疫的负调节，例如肿瘤微环境中的效应T细胞耗竭。然而，诱导和预防T细胞耗竭的机制在很大程度上仍然未知。我们发现，CD 69是一种II型糖蛋白，已知通过T细胞迁移和组织中的滞留来调节炎症，在诱导肿瘤浸润性T细胞的耗竭中起重要作用。在4 T1-luc 2小鼠乳腺癌模型中，Cd 69（-/-）小鼠显示肿瘤生长和转移减少，其中观察到肿瘤浸润淋巴细胞数量增加，T细胞耗竭相对较少，IFN γ产生增加。抗-CD 69单克隆抗体治疗减弱了荷瘤小鼠中的T细胞耗竭和肿瘤进展。这些发现突出了CD 69在控制由T细胞耗竭介导的肿瘤免疫逃逸中的新作用，并表明CD 69是癌症免疫治疗的新靶点。
The introduction of immune checkpoint inhibitors in cancer treatment highlights the negative regulation of anti-tumor immunity, such as effector T-cell exhaustion in the tumor microenvironment. However, the mechanisms underlying the induction and prevention of T-cell exhaustion remain largely unknown. We found that CD69, a type II glycoprotein known to regulate inflammation through T-cell migration and retention in tissues, plays an important role in inducing the exhaustion of tumor-infiltrating T cells. Cd69(-/-) mice showed reduced tumor growth and metastasis in a 4T1-luc2 murine breast cancer model, in which increased numbers of tumor-infiltrating lymphocytes, relatively little T-cell exhaustion, and enhanced IFN gamma production were observed. Anti-CD69 monoclonal antibody treatment attenuated the T-cell exhaustion and tumor progression in tumor-bearing mice. These findings highlight a novel role of CD69 in controlling the tumor immune escape mediated by T-cell exhaustion and indicate that CD69 is a novel target for cancer immunotherapy.