Mycobacterium smegmatis enhances shikonin-induced immunogenic cell death—an efficient in situ tumor vaccine strategy  

作　　者：Zhaoye Qian Zhe Zhang Lanqi Cen Yaohua Ke Jie Shao Manman Tian Baorui Liu 

机构地区：[1]Department of Oncology,Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University,Nanjing,Jiangsu 210008,China [2]Department of Oncology,the Affiliated Huai'an No.1 People's Hospital,Nanjing Medical University,Huai'an,Jiangsu 223000,China [3]Center of Clinical Oncology,the Affiliated Hospital of Xuzhou Medical University,Xuzhou,Jiangsu 221000,China [4]Department of Oncology,China Pharmaceutical University Nanjing Drum Tower Hospital,Nanjing,Jiangsu 210008,China [5]The Comprehensive Cancer Center,Nanjing Drum Tower Hospital,Affiliated Hospital of Medical School,Nanjing University,Nanjing,Jiangsu 210008,China [6]Department of Oncology,Nanjing Drum Tower Hospital,Affiliated Hospital of Medical School,Nanjing University,Nanjing,Jiangsu 210008,China

出　　处：《Journal of Biomedical Research》2024年第4期369-381,共13页生物医学研究杂志（英文版）

基　　金：supported by grants from the Natural Science Foundation of Huai'an Science and Technology Bureau(Grant No.HAB202312);the Science and Technology Development Fund of the Affiliated Hospital of Xuzhou Medical University(Grant No.XYFY2021018).

摘　　要：Tumor vaccines are a promising avenue in cancer immunotherapy.Despite the progress in targeting specific immune epitopes,tumor cells lacking these epitopes can evade the treatment.Here,we aimed to construct an efficient in situ tumor vaccine called Vac-SM,utilizing shikonin(SKN)to induce immunogenic cell death(ICD)and Mycobacterium smegmatis as an immune adjuvant to enhance in situ tumor vaccine efficacy.SKN showed a dose-dependent and time-dependent cytotoxic effect on the tumor cell line and induced ICD in tumor cells as evidenced by the CCK-8 assay and the detection of the expression of relevant indicators,respectively.Compared with the control group,the in situ Vac-SM injection in mouse subcutaneous metastatic tumors significantly inhibited tumor growth and distant tumor metastasis,while also improving survival rates.Mycobacterium smegmatis effectively induced maturation and activation of bone marrow-derived dendritic cells(DCs),and in vivo tumor-draining lymph nodes showed an increased maturation of DCs and a higher proportion of effector memory T-cell subsets with the Vac-SM treatment,based on flow cytometry analysis results.Collectively,the Vac-SM vaccine effectively induces ICD,improves antigen presentation by DCs,activates a specific systemic antitumor T-cell immune response,exhibits a favorable safety profile,and holds the promise for clinical translation for local tumor immunotherapy.

关 键 词：MYCOBACTERIUM SMEGMATIS SHIKONIN IMMUNOGENIC cell death tumor vaccines IMMUNOGENICITY CYTOTOXICITY 

分 类 号：R730.51[医药卫生—肿瘤]