Mycobacterium smegmatis enhances shikonin-induced immunogenic cell death—an efficient in situ tumor vaccine strategy
Zhaoye Qian1
Zhe Zhang2
Lanqi Cen3
Yaohua Ke4
Jie Shao5
Manman Tian5
Baorui Liu6
1.Department of Oncology,Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University,Nanjing,Jiangsu 210008,China;Department of Oncology,the Affiliated Huai'an No.1 People's Hospital,Nanjing Medical University,Huai'an,Jiangsu 223000,China2.Center of Clinical Oncology,the Affiliated Hospital of Xuzhou Medical University,Xuzhou,Jiangsu 221000,China3.Department of Oncology,China Pharmaceutical University Nanjing Drum Tower Hospital,Nanjing,Jiangsu 210008,China4.The Comprehensive Cancer Center,Nanjing Drum Tower Hospital,Affiliated Hospital of Medical School,Nanjing University,Nanjing,Jiangsu 210008,China5.Department of Oncology,Nanjing Drum Tower Hospital,Affiliated Hospital of Medical School,Nanjing University,Nanjing,Jiangsu 210008,China6.Department of Oncology,Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University,Nanjing,Jiangsu 210008,China;The Comprehensive Cancer Center,Nanjing Drum Tower Hospital,Affiliated Hospital of Medical School,Nanjing University,Nanjing,Jiangsu 210008,China;Department of Oncology,Nanjing Drum Tower Hospital,Affiliated Hospital of Medical School,Nanjing University,Nanjing,Jiangsu 210008,China
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.
机标关键词：strategytumorcelldeathefficientenhancesimmunogenicinduced
分类号：R730.51(一般性问题)
论文发表日期：2024-07-30
在线出版日期：2026-03-31（本平台首次上网日期，不代表文献的发表时间）
页数：14( 中插7,369-381 )
英文信息