标题：STAT3-blocked whole-cell hepatoma vaccine induces cellular and humoral immune response against HCC
作者：Han, Qiuju; Wang, Yaqun; Pang, Min; Zhang, Jian
作者机构：[Han, Qiuju; Wang, Yaqun; Pang, Min; Zhang, Jian] Shandong Univ, Inst Immunopharmaceut Sci, Sch Pharmaceut Sci, Jinan 250012, Shandong, Peoples R Chin 更多
通讯作者地址：[Zhang, J]Shandong Univ, Inst Immunopharmaceut Sci, Sch Pharmaceut Sci, Jinan 250012, Shandong, Peoples R China.
来源：JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
关键词：Tumor vaccine; STAT3; Hepatoma; Immunotherapy; Whole-cell vaccine
摘要：Background: 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.; Methods: 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.; Results: 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-beta 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.; Conclusions: The newly generated STAT3-blocked whole-cell HCC vaccine has potential for cancer cell vaccination.