Li Yan, He Lianghua, Dong Haiqing, Liu Yiqiong, Wang Kun, Li Ang, Ren Tianbin, Shi Donglu, Li Yongyong
Shanghai East Hospital The Institute for Biomedical Engineering and Nano Science Tongji University School of Medicine Shanghai 200092 P. R. China.
School of Materials Science and Engineering Tongji University 4800 Caoan Road Shanghai 201804 P. R. China.
Adv Sci (Weinh). 2018 Mar 25;5(6):1700805. doi: 10.1002/advs.201700805. eCollection 2018 Jun.
Although there have been more than 100 clinical trials, CpG-based immunotherapy has been seriously hindered by complications in the immunosuppressive microenvironment of established tumors. Inspired by the decisive role of fever upon systemic immunity, a photothermal CpG nanotherapeutics (PCN) method with the capability to induce an immunofavorable tumor microenvironment by casting a fever-relevant heat (43 °C) in the tumor region is developed. High-throughput gene profile analysis identifies nine differentially expressed genes that are closely immune-related upon mild heat, accompanied by IL-6 upregulation, a pyrogenic cytokine usually found during fever. When treated with intratumor PCN injection enabling mild heating in the tumor region, the 4T1 tumor-bearing mice exhibit significantly improved antitumor immune effects compared with the control group. Superb efficacy is evident from pronounced apoptotic cell death, activated innate immune cells, enhanced tumor perfusion, and intensified innate and adaptive immune responses. This work highlights the crucial role of mild heat in modulating the microenvironment in optimum for improved immunotherapy, by converting the tumor into an in situ vaccine.
尽管已经进行了100多项临床试验，但基于CpG的免疫疗法在已形成肿瘤的免疫抑制微环境中受到并发症的严重阻碍。受发热对全身免疫的决定性作用启发，开发了一种光热CpG纳米疗法（PCN），该方法能够通过在肿瘤区域施加与发热相关的热量（43°C）来诱导免疫有利的肿瘤微环境。高通量基因谱分析确定了九个在轻度加热时与免疫密切相关的差异表达基因，同时伴有IL-6上调，IL-6是一种通常在发热期间发现的致热细胞因子。当通过肿瘤内注射PCN使肿瘤区域轻度加热时，与对照组相比，荷4T1肿瘤小鼠表现出显著改善的抗肿瘤免疫效果。明显的凋亡细胞死亡、激活的先天免疫细胞、增强的肿瘤灌注以及强化的先天和适应性免疫反应都证明了其卓越的疗效。这项工作强调了轻度加热在调节微环境以实现最佳免疫治疗方面的关键作用，即将肿瘤转化为原位疫苗。
