STAT3-blocked whole-cell hepatoma vaccine induces cellular and humoral immune response against HCC.
STAT3-blocked whole-cell hepatoma vaccine induces cellular and humoral immune response against HCC.
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STAT3阻断的全细胞肝癌疫苗诱导针对HCC的细胞和体液免疫反应
DOI：
10.1186/s13046-017-0623-0
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发表时间：
2017-11-07
期刊：
影响因子：
--
通讯作者：
Zhang J
中科院分区：
文献类型：
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作者：
Han Q;Wang Y;Pang M;Zhang J
全细胞肿瘤疫苗已经显示出很大的前景；然而，在激发强大的肿瘤特异性T细胞反应的目标方面，只取得了有限的成功。用STAT3诱骗寡核苷酸对肝癌细胞H22和Hepa1-6进行STAT3信号通路的修饰，并对其免疫原性和作为疫苗的可能性进行了评价。STAT3封闭的整个肝癌细胞裂解物抑制肿瘤生长和成瘤，延长荷瘤小鼠的生存时间。此外，STAT3封闭的整个肝癌细胞裂解物刺激T细胞和自然杀伤(NK)细胞的激活，并增强细胞毒CD8+T细胞在肿瘤组织中的渗透。此外，树突状细胞(DC)的成熟增强，促进了抗肝癌免疫记忆的产生。此外，这些免疫小鼠一旦被肝癌细胞攻击，即可启动二次免疫应答，并伴随着T细胞和NK细胞的激活和浸润。此外，用该疫苗免疫可减少Treg的产生以及转化生长因子-β和IL-10的产生。重要的是，STAT3封闭的整个肝癌细胞裂解物阻止了肝癌介导的T细胞和NK细胞的耗竭，在免疫小鼠的T细胞和NK细胞上显示出低表达的检查点分子，如PD-1和TIGIT。新产生的STAT3阻断的全细胞肝癌疫苗具有接种癌细胞的潜力。本文的在线版本(10.1186/s13046-0170623-0)包含补充材料，可供授权用户使用。
Whole-cell tumor vaccines have shown much promise; however, only limited success has been achieved for the goal of eliciting robust tumor-specific T-cell responses. Hepatocellular carcinoma (HCC) cells, H22 and Hepa1–6, were modified by blocking the STAT3 signaling pathway with a STAT3 decoy oligodeoxynucleotide, and the immunogenicity and possibility of using these cell lysates as a vaccine were evaluated. STAT3-blocked whole HCC cell lysates inhibited tumor growth and tumorigenesis, and prolonged the survival of tumor-bearing mice. In addition, STAT3-blocked whole HCC cell lysates stimulated the activation of T cells and natural killer (NK) cells, and enhanced the infiltration of cytotoxic CD8+ T cells in the tumor tissues. In addition, the maturation of dendritic cells (DCs) was enhanced, which promoted the generation of immunological memory against HCC. Furthermore, secondary immune responses could be primed as soon as these immunized mice were challenged with HCC cells, accompanied by T cell and NK cell activation and infiltration. Additionally, immunization with this vaccine decreased the generation of Tregs and the production of TGF-β and IL-10. Importantly, STAT3-blocked whole HCC cell lysates prevented HCC-mediated exhaustion of T cells and NK cells, showing low expression of checkpoint molecules such as PD-1 and TIGIT on T cells and NK cells in the immunized mice. The newly generated STAT3-blocked whole-cell HCC vaccine has potential for cancer cell vaccination. The online version of this article (10.1186/s13046-017-0623-0) contains supplementary material, which is available to authorized users.