Fever-Inspired Immunotherapy Based on Photothermal CpG Nanotherapeutics: The Critical Role of Mild Heat in Regulating Tumor Microenvironment.
Fever-Inspired Immunotherapy Based on Photothermal CpG Nanotherapeutics: The Critical Role of Mild Heat in Regulating Tumor Microenvironment.
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基于光热 CpG 纳米疗法的发热免疫疗法：温和的热量在调节肿瘤微环境中的关键作用
DOI：
10.1002/advs.201700805
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发表时间：
2018-06
期刊：
影响因子：
--
通讯作者：
Li Y
中科院分区：
文献类型：
--
作者：
Li Y;He L;Dong H;Liu Y;Wang K;Li A;Ren T;Shi D;Li Y
尽管已经有100多项临床试验，但基于CpG的免疫治疗受到已建立肿瘤免疫抑制微环境中并发症的严重阻碍。受发热对全身免疫的决定性作用的启发，开发了一种光热CpG纳米治疗（PCN）方法，该方法能够通过在肿瘤区域投射发热相关的热量（43 °C）来诱导免疫保护的肿瘤微环境。高通量基因谱分析确定了9个差异表达的基因，这些基因在轻度发热时与免疫密切相关，并伴有IL-6上调，这是一种通常在发热期间发现的致热原细胞因子。与对照组相比，4 T1荷瘤小鼠在瘤内注射PCN（可在肿瘤区域进行轻度加热）治疗时，抗肿瘤免疫效果显著改善。显著的凋亡性细胞死亡、激活的先天性免疫细胞、增强的肿瘤灌注以及增强的先天性和适应性免疫应答证明了极好的疗效。这项工作强调了温和的热量在调节微环境中的关键作用，通过将肿瘤转化为原位疫苗来改善免疫治疗。
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.
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