4.6

CiteScore

2.2

Impact Factor
  • ISSN 1674-8301
  • CN 32-1810/R
Zhaoye Qian, Zhe Zhang, Lanqi Cen, Yaohua Ke, Jie Shao, Manman Tian, Baorui Liu. Mycobacterium smegmatis enhances shikonin-induced immunogenic cell death—an efficient in situ tumor vaccine strategy[J]. The Journal of Biomedical Research, 2024, 38(4): 369-381. DOI: 10.7555/JBR.38.20240049
Citation: Zhaoye Qian, Zhe Zhang, Lanqi Cen, Yaohua Ke, Jie Shao, Manman Tian, Baorui Liu. Mycobacterium smegmatis enhances shikonin-induced immunogenic cell death—an efficient in situ tumor vaccine strategy[J]. The Journal of Biomedical Research, 2024, 38(4): 369-381. DOI: 10.7555/JBR.38.20240049

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

More Information
  • Corresponding author:

    Baorui Liu, Department of Oncology, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, 321 Zhongshan Road, Nanjing, Jiangsu 210008, China. E-mail: baoruiliu@nju.edu.cn

  • △These authors contributed equally to this work.

  • Received Date: February 24, 2024
  • Revised Date: April 16, 2024
  • Accepted Date: April 29, 2024
  • Available Online: May 13, 2024
  • Published Date: May 28, 2024
  • 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.

  • None.

    The present study was supported by grants from the Natural Science Foundation of Huai'an Science and Technology Bureau (Grant No. HAB202312) and the Science and Technology Development Fund of the Affiliated Hospital of Xuzhou Medical University (Grant No. XYFY2021018).

    CLC number: R730.51, Document code: A

    The authors reported no conflict of interests.

  • [1]
    Lin MJ, Svensson-Arvelund J, Lubitz GS, et al. Cancer vaccines: the next immunotherapy frontier[J]. Nat Cancer, 2022, 3(8): 911–926. doi: 10.1038/s43018-022-00418-6
    [2]
    Fan T, Zhang M, Yang J, et al. Therapeutic cancer vaccines: advancements, challenges, and prospects[J]. Signal Transduct Target Ther, 2023, 8(1): 450. doi: 10.1038/s41392-023-01674-3
    [3]
    Lancaster EM, Jablons D, Kratz JR. Applications of next-generation sequencing in neoantigen prediction and cancer vaccine development[J]. Genet Test Mol Biomarkers, 2020, 24(2): 59–66. doi: 10.1089/gtmb.2018.0211
    [4]
    Fennemann FL, de Vries IJM, Figdor CG, et al. Attacking tumors from all sides: personalized multiplex vaccines to tackle intratumor heterogeneity[J]. Front Immunol, 2019, 10: 824. doi: 10.3389/fimmu.2019.00824
    [5]
    Lurje I, Werner W, Mohr R, et al. In situ vaccination as a strategy to modulate the immune microenvironment of hepatocellular carcinoma[J]. Front Immunol, 2021, 12: 650486. doi: 10.3389/fimmu.2021.650486
    [6]
    Bijker MS, van den Eeden SJF, Franken KL, et al. Superior induction of anti-tumor CTL immunity by extended peptide vaccines involves prolonged, DC-focused antigen presentation[J]. Eur J Immunol, 2008, 38(4): 1033–1042. doi: 10.1002/eji.200737995
    [7]
    Galluzzi L, Vitale I, Warren S, et al. Consensus guidelines for the definition, detection and interpretation of immunogenic cell death[J]. J Immunother Cancer, 2020, 8(1): e000337. doi: 10.1136/jitc-2019-000337
    [8]
    Ahmed A, Tait SWG. Targeting immunogenic cell death in cancer[J]. Mol Oncol, 2020, 14(12): 2994–3006. doi: 10.1002/1878-0261.12851
    [9]
    Calvillo-Rodríguez KM, Lorenzo-Anota HY, Rodríguez-Padilla C, et al. Immunotherapies inducing immunogenic cell death in cancer: insight of the innate immune system[J]. Front Immunol, 2023, 14: 1294434. doi: 10.3389/fimmu.2023.1294434
    [10]
    Kazumura K, Yoshida LS, Hara A, et al. Inhibition of neutrophil superoxide generation by shikonin is associated with suppression of cellular Ca2+ fluxes[J]. J Clin Biochem Nutr, 2016, 59(1): 1–9. doi: 10.3164/jcbn.16-4
    [11]
    Yu Z, Liu Y, Zhu J, et al. Insights from molecular dynamics simulations and steered molecular dynamics simulations to exploit new trends of the interaction between HIF-1α and p300[J]. J Biomol Struct Dyn, 2020, 38(1): 1–12. doi: 10.1080/07391102.2019.1580616
    [12]
    Gupta B, Chakraborty S, Saha S, et al. Antinociceptive properties of shikonin: in vitro and in vivo studies[J]. Can J Physiol Pharmacol, 2016, 94(7): 788–796. doi: 10.1139/cjpp-2015-0465
    [13]
    Guo T, Jiang Z, Tong Z, et al. Shikonin ameliorates LPS-induced cardiac dysfunction by SIRT1-dependent inhibition of NLRP3 inflammasome[J]. Front Physiol, 2020, 11: 570441. doi: 10.3389/fphys.2020.570441
    [14]
    Gan L, Wang Z, Zhang H, et al. Protective effects of shikonin on brain injury induced by carbon ion beam irradiation in mice[J]. Biomed Environ Sci, 2015, 28(2): 148–151. doi: 10.3967/bes2015.019
    [15]
    Bergamaschi D, Vossenkamper A, Lee WYJ, et al. Simultaneous polychromatic flow cytometric detection of multiple forms of regulated cell death[J]. Apoptosis, 2019, 24(5-6): 453–464. doi: 10.1007/s10495-019-01528-w
    [16]
    Song J, Zhao Z, Fan X, et al. Shikonin potentiates the effect of arsenic trioxide against human hepatocellular carcinoma in vitro and in vivo[J]. Oncotarget, 2016, 7(43): 70504–70515. doi: 10.18632/oncotarget.12041
    [17]
    He G, He G, Zhou R, et al. Enhancement of cisplatin-induced colon cancer cells apoptosis by shikonin, a natural inducer of ROS in vitro and in vivo[J]. Biochem Biophys Res Commun, 2016, 469(4): 1075–1082. doi: 10.1016/j.bbrc.2015.12.100
    [18]
    Chen H, Wang PH, Chen SS, et al. Shikonin induces immunogenic cell death in tumor cells and enhances dendritic cell-based cancer vaccine[J]. Cancer Immunol Immunother, 2012, 61(11): 1989–2002. doi: 10.1007/s00262-012-1258-9
    [19]
    Fitzgerald KA, Kagan JC. Toll-like receptors and the control of immunity[J]. Cell, 2020, 180(6): 1044–1066. doi: 10.1016/j.cell.2020.02.041
    [20]
    Lamensans A, Chedid L, Lederer E, et al. Enhancement of immunity against murine syngeneic tumors by a fraction extracted from non-pathogenic mycobacteria[J]. Proc Natl Acad Sci USA, 1975, 72(9): 3656–3660. doi: 10.1073/pnas.72.9.3656
    [21]
    Yarkoni E, Rapp HJ. Immunotherapy of experimental cancer by intralesional injection of emulsified nonliving mycobacteria: comparison of Mycobacterium bovis (BCG), Mycobacterium phlei, and Mycobacterium smegmatis[J]. Infect Immun, 1980, 28(3): 887–892. doi: 10.1128/iai.28.3.887-892.1980
    [22]
    Rich FJ, Kuhn S, Hyde EJ, et al. Induction of T cell responses and recruitment of an inflammatory dendritic cell subset following tumor immunotherapy with Mycobacterium smegmatis[J]. Cancer Immunol Immunother, 2012, 61(12): 2333–2342. doi: 10.1007/s00262-012-1291-8
    [23]
    Garg AD, Galluzzi L, Apetoh L, et al. Molecular and translational classifications of DAMPs in immunogenic cell death[J]. Front Immunol, 2015, 6: 588. doi: 10.3389/fimmu.2015.00588
    [24]
    Li J, Zhou S, Yu J, et al. Low dose shikonin and anthracyclines coloaded liposomes induce robust immunogenetic cell death for synergistic chemo-immunotherapy[J]. J Control Release, 2021, 335: 306–319. doi: 10.1016/j.jconrel.2021.05.040
    [25]
    François V, Ottaviani S, Renkvist N, et al. The CD4+ T-cell response of melanoma patients to a MAGE-A3 peptide vaccine involves potential regulatory T cells[J]. Cancer Res, 2009, 69(10): 4335–4345. doi: 10.1158/0008-5472.CAN-08-3726
    [26]
    Ott PA, Hu-Lieskovan S, Chmielowski B, et al. A phase Ib trial of personalized neoantigen therapy plus anti-PD-1 in patients with advanced melanoma, non-small cell lung cancer, or bladder cancer[J]. Cell, 2020, 183(2): 347–362. e24.
    [27]
    Hammerich L, Bhardwaj N, Kohrt HE, et al. In situ vaccination for the treatment of cancer[J]. Immunotherapy, 2016, 8(3): 315–330. doi: 10.2217/imt.15.120
    [28]
    Ke Y, Zhu J, Chu Y, et al. Bifunctional fusion membrane-based hydrogel enhances antitumor potency of autologous cancer vaccines by activating dendritic cells[J]. Adv Funct Mater, 2022, 32(29): 2201306. doi: 10.1002/adfm.202201306
    [29]
    Soares KC, Rucki AA, Wu AA, et al. PD-1/PD-L1 blockade together with vaccine therapy facilitates effector T-cell infiltration into pancreatic tumors[J]. J Immunother, 2015, 38(1): 1–11. doi: 10.1097/CJI.0000000000000062
    [30]
    Yang SF, Weng MT, Liang JD, et al. Neoantigen vaccination augments antitumor effects of anti-PD-1 on mouse hepatocellular carcinoma[J]. Cancer Lett, 2023, 563: 216192. doi: 10.1016/j.canlet.2023.216192
    [31]
    Shan C, Du Y, Zhai X, et al. Pingyangmycin enhances the antitumor efficacy of anti-PD-1 therapy associated with tumor-infiltrating CD8+ T cell augmentation[J]. Cancer Chemother Pharmacol, 2021, 87(3): 425–436. doi: 10.1007/s00280-020-04209-7
  • Related Articles

    [1]Pavan Kumar Dhanyamraju, Trupti N. Patel. Melanoma therapeutics: a literature review[J]. The Journal of Biomedical Research, 2022, 36(2): 77-97. DOI: 10.7555/JBR.36.20210163
    [2]Yoon Su Young, Kim Si-Wook, Kim Dohun, Hong Jong-Myeon. Contained local compression on peri-ascending aortic area for postoperative bleeding control: a case report[J]. The Journal of Biomedical Research, 2021, 35(1): 72-74. DOI: 10.7555/JBR.34.20200085
    [3]Yang Lukun, Tautz Timothy, Zhang Shulin, Fomina Alla, Liu Hong. The current status of malignant hyperthermia[J]. The Journal of Biomedical Research, 2020, 34(2): 75-85. DOI: 10.7555/JBR.33.20180089
    [4]Didi Zhu, Jiamin Yuan, Rui Zhu, Yao Wang, Zhiyong Qian, Jiangang Zou. Pathway-based analysis of genome-wide association study of circadian phenotypes[J]. The Journal of Biomedical Research, 2018, 32(5): 361-370. DOI: 10.7555/JBR.32.20170102
    [5]Sang-Yong Eom, Dong-Hyuk Yim, Jung-Hyun Kim, Joo-Byung Chae, Yong-Dae Kim, Heon Kim. A pilot exome-wide association study of age-related cataract in Koreans[J]. The Journal of Biomedical Research, 2016, 30(3): 186-190. DOI: 10.7555/JBR.30.2016K0002
    [6]Shaoli Wang, Jingyun Zhang, Tao Sheng, Wei Lu, Dengshun Miao. Hippocampal ischemia causes deficits in local field potential and synaptic plasticity[J]. The Journal of Biomedical Research, 2015, 29(5): 370-379. DOI: 10.7555/JBR.29.20150010
    [7]Ping Zeng, Yang Zhao, Cheng Qian, Liwei Zhang, Ruyang Zhang, Jianwei Gou, Jin Liu, Liya Liu, Feng Chen. Statistical analysis for genome-wide association study[J]. The Journal of Biomedical Research, 2015, 29(4): 285-297. DOI: 10.7555/JBR.29.20140007
    [8]Chih-Kun Huang, Amit Garg, Hsin-Chih Kuao, Po-Chih Chang, Ming-Che Hsin. Bariatric surgery in old age: a comparative study of laparoscopic Roux-en-Y gastric bypass and sleeve gastrectomy in an Asia centre of excellence[J]. The Journal of Biomedical Research, 2015, 29(2): 118-124. DOI: 10.7555/JBR.29.20140108
    [9]Yaomin Zhu, Guixia Jing, Wei Yuan. Preoperative administration of intramuscular dezocine reduces postoperative pain for laparoscopic cholecystectomy[J]. The Journal of Biomedical Research, 2011, 25(5): 356-361. DOI: 10.1016/S1674-8301(11)60047-X
    [10]Yangyang Zhang, Yanhu Wu, Biao Yuan, Xiang Liu, Sheng Zhao, Zhi Li, Yu Xia. Coronary artery bypass grafting with concomitant resection for carcinoma of lung[J]. The Journal of Biomedical Research, 2010, 24(1): 77-80.
  • Cited by

    Periodical cited type(6)

    1. Paolino G, Podo Brunetti A, De Rosa C, et al. Anorectal melanoma: systematic review of the current literature of an aggressive type of melanoma. Melanoma Res, 2024, 34(6): 487-496. DOI:10.1097/CMR.0000000000001003
    2. Illa SK, Mumtaz S, Nath S, et al. Characterization of runs of Homozygosity revealed genomic inbreeding and patterns of selection in indigenous sahiwal cattle. J Appl Genet, 2024, 65(1): 167-180. DOI:10.1007/s13353-023-00816-1
    3. Ugonabo O, Mohamed M, Ezeh E, et al. A Rare Metastatic Primary Rectal Melanoma in a Geriatric Male. J Med Cases, 2022, 13(8): 369-373. DOI:10.14740/jmc3929
    4. Si M, Cao X. Considering Computational Mathematics IGHG3 as Malignant Melanoma Is Associated with Immune Infiltration of Malignant Melanoma. Biomed Res Int, 2022, 2022: 4168937. DOI:10.1155/2022/4168937
    5. Nonaka K, Kudou K, Sasaki S, et al. Primary anorectal malignant melanoma with laparoscopic abdominoperineal resection: a case study and review of the relevant literature. Int Cancer Conf J, 2020, 9(3): 116-122. DOI:10.1007/s13691-020-00401-x
    6. Heo JR, Hwang KA, Kim SU, et al. A Potential Therapy Using Engineered Stem Cells Prevented Malignant Melanoma in Cellular and Xenograft Mouse Models. Cancer Res Treat, 2019, 51(2): 797-811. DOI:10.4143/crt.2018.364

    Other cited types(0)

Catalog

    Figures(6)

    Article Metrics

    Article views (705) PDF downloads (181) Cited by(6)
    Related

    /

    DownLoad:  Full-Size Img  PowerPoint
    Return
    Return