Virus-specific memory T cells populate tumors and can be repurposed for tumor immunotherapy
Virus-specific memory T cells populate tumors and can be repurposed for tumor immunotherapy
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DOI：
10.1038/s41467-019-08534-1
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发表时间：
2019-02-04
影响因子：
16.6
通讯作者：
Masopust, David
中科院分区：
文献类型：
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作者：
Rosato, Pamela C.;Wijeyesinghe, Sathi;Masopust, David
免疫抑制的肿瘤微环境限制了当前免疫治疗的成功。宿主保留着记忆T细胞，这些T细胞能够在整个身体内执行强大的和立即的免疫刺激功能，对以前的感染具有特异性。在这里，我们展示了病毒特异性记忆T细胞将他们的监测扩展到老鼠和人类的肿瘤。在将无佐剂、非复制的病毒多肽注射到肿瘤中后，重新激活这些抗病毒T细胞可以阻止小鼠体内检查点阻断抵抗和免疫原性差的肿瘤的生长。多肽模拟病毒再感染事件来记忆CD8+T细胞，触发肿瘤内的抗原递呈和细胞毒途径，激活树突状细胞和自然杀伤细胞，并招募适应性免疫系统。体外人类肿瘤的病毒多肽治疗概括了在小鼠中观察到的免疫激活基因表达谱。最后，多肽治疗使耐药小鼠肿瘤容易受到PD-L1阻断的影响。因此，重新刺激已知的抗病毒免疫可能为癌症免疫治疗提供一种独特的治疗方法。
The immunosuppressive tumor microenvironment limits the success of current immunotherapies. The host retains memory T cells specific for previous infections throughout the entire body that are capable of executing potent and immediate immunostimulatory functions. Here we show that virus-specific memory T cells extend their surveillance to mouse and human tumors. Reactivating these antiviral T cells can arrest growth of checkpoint blockade-resistant and poorly immunogenic tumors in mice after injecting adjuvant-free non-replicating viral peptides into tumors. Peptide mimics a viral reinfection event to memory CD8+ T cells, triggering antigen presentation and cytotoxic pathways within the tumor, activating dendritic cells and natural killer cells, and recruiting the adaptive immune system. Viral peptide treatment of ex vivo human tumors recapitulates immune activation gene expression profiles observed in mice. Lastly, peptide therapy renders resistant mouse tumors susceptible to PD-L1 blockade. Thus, re-stimulating known antiviral immunity may provide a unique therapeutic approach for cancer immunotherapy.