Dendritic Cell Immunotherapy Combined with Cytokine-Induced Killer Cells Effectively Suppresses Established Hepatocellular Carcinomas in Mice

Jung, Nam-Chul; Lee, Jun-Ho; Choi, Hojung; Hwang, Sung-Uk; Song, Jie‐Young; Seo, Han Geuk; Choi, Jinjung; Jung, Sang Youn; Han, Sung Gu; Lim, Dae‐Seog

doi:10.1080/08820139.2016.1183025

Cited by 15 publications

(9 citation statements)

References 27 publications

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“…We also observed enhanced DC antigen presentation ability by employing a DC and CIK co-culture. Jung et al demonstrated that DC-induced CIK cells could effectively inhibit the growth of HCC MH134 in a mouse model of liver cancer ( 28 ). Animal experiments have confirmed that MIP-3α can efficiently attract DCs into mouse liver cancer lesions to inhibit tumor growth ( 29 ).…”

Section: Discussionmentioning

confidence: 99%

RETRACTED: The Collective Effect of MIP-3α and FL Promotes Dendritic Cell Function Within the Immune Microenvironment of Murine Liver Cancer

Zhao

Chen

et al. 2021

Front. Oncol.

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Hepatocellular carcinoma is a highly malignant and lethal tumor. In addition to surgery, immunotherapy is currently a more effective treatment for hepatocellular carcinoma. The tumor immune microenvironment (TIME) largely determines the efficacy of cancer immunotherapy. Based on the universal targeting of TIME modulators in clinical treatment, TIME modulators are promising targets for tumor immunotherapy. We investigated the effect of a double gene expression vector (recombinant galactose-terminal glycol-poly-L-lysine coupled MIP-3α-FL) on dendritic cells (DCs) regulation within the TIME of mice with liver cancer. H22 cells were transfected with a recombinant MIP-3α-FL plasmid to induce DCs differentiation and chemotaxis. The effects of transfection were investigated by flow cytometry following the modified Boyden’s method. Cytokine-induced killer (CIK) cells co-culture revealed changes in the antigen presentation ability of DCs. Further, tumor-bearing mice were injected with the recombinant double gene vector via the tail vein. We compared the survival time, tumor volume, weight of the mice, as well as the number and phenotype of tumor-infiltrating DCs (TIDCs) between groups. The supernatant of transfected H22 cells promoted the phenotypic maturation of DCs, enhancing their chemotaxis. Further, treated DCs promoted the cytokine secretion and killing ability of CIK cells. The survival time of mice injected with the double gene vector was significantly prolonged, while their tumor weight and volume were relatively reduced. Flow cytometry revealed that the number of TIDCs (as well as CD80 and CD86 expression) in the MouseMIP-3α-FL group, were significantly higher than in the control group. The combination of MIP-3α and FL can significantly promote DCs aggregation, maturation, and enhance their antigen presentation ability. The coupling of the double gene vector with glycosylated polylysine can improve the precise targeting of the liver and inhibit tumor growth in vivo, providing a novel approach for immune therapy in liver cancer.

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Section: Discussionmentioning

confidence: 99%

RETRACTED: The Collective Effect of MIP-3α and FL Promotes Dendritic Cell Function Within the Immune Microenvironment of Murine Liver Cancer

Zhao

Chen

et al. 2021

Front. Oncol.

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“…In mice, DC immunotherapy combined with cytokine-induced killer cells suppresses established HCC. 80…”

Section: Hdcs and Immune Escape In Hepatocellular Carcinomamentioning

confidence: 99%

Hepatic Dendritic Cells, the Tolerogenic Liver Environment, and Liver Disease

et al. 2018

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The unique liver immune microenvironment favors resistance to inflammation that promotes normal physiological function. At the same time, it endows the liver with tolerogenic properties that may promote pathological processes. Hepatic dendritic cells (HDCs) initiate and orchestrate immune responses depending on signals they receive from the local environment and are thought to contribute to liver tolerance. Thus, HDCs facilitate impaired T cell responses that are observed in persistent hepatitis C virus (HCV) infection, hepatocellular carcinoma progression, and liver allograft transplantation. HDCs also participate in anti-inflammatory responses in liver ischemia-reperfusion injury (IRI). Moreover, they promote the regression of fibrosis from various fibrogenic liver injuries. These findings suggest that HDCs regulate intrahepatic immune responses, allowing the liver to maintain homeostasis and integrity even under pathological conditions. This review focuses on the tolerogenic properties of HDCs based on recent research and in relation to liver disease pathogenesis and its therapy.

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“…Preclinical and clinical models in which ex vivo -expanded CIK cells have been tested also demonstrate antitumor activity, but only modest therapeutic efficacy; this is due largely to the strategies used by tumors to evade the host immune system [52] . To overcome these problems, we wondered whether a combination of DC vaccination plus CIK cells would induce a stronger therapeutic antitumor effect than administration of DCs or CIK cells alone [54] .…”

Section: Immunotherapy Combined With Cytokine-induced Killer (Cik)mentioning

confidence: 99%

“…Our previous report demonstrated that DC vaccination combined with adoptive transfer of CIK cells leads to significant suppression of hepatoma tumor cell growth and improved antitumor responses [54] . These results suggest that a combination of DCs plus CIK cells can increase antitumor activity, indicating a potential for clinical application to cancer patients in the future.…”

Section: Immunotherapy Combined With Cytokine-induced Killer (Cik)mentioning

confidence: 99%

Dendritic Cell-Based Immunotherapy for Solid Tumors

Jung

Lee

Chung

et al. 2018

Translational Oncology

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As a treatment for solid tumors, dendritic cell (DC)-based immunotherapy has not been as effective as expected. Here, we review the reasons underlying the limitations of DC-based immunotherapy for solid tumors and ask what can be done to improve immune cell-based cancer therapies. Several reports show that, rather than a lack of immune induction, the limited efficacy of DC-based immunotherapy in cases of renal cell carcinoma (RCC) likely results from inhibition of immune responses by tumor-secreted TGF-β and an increase in the number of regulatory T (Treg) cells in and around the solid tumor. Indeed, unlike DC therapy for solid tumors, cytotoxic T lymphocyte (CTL) responses induced by DC therapy inhibit tumor recurrence after surgery; CTL responses also limit tumor metastasis induced by additional tumor-challenge in RCC tumor-bearing mice. Here, we discuss the mechanisms underlying the poor efficacy of DC-based therapy for solid tumors and stress the need for new and improved DC immunotherapies and/or combination therapies with killer cells to treat resistant solid tumors.

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Dendritic Cell Immunotherapy Combined with Cytokine-Induced Killer Cells Effectively Suppresses Established Hepatocellular Carcinomas in Mice

Abstract: Taken together, these results show that a DC + CIK vaccination is more effective than DC or CIK alone therapy for the treatment of hepatocarcinoma cancer.

Cited by 15 publications

References 27 publications

RETRACTED: The Collective Effect of MIP-3α and FL Promotes Dendritic Cell Function Within the Immune Microenvironment of Murine Liver Cancer

RETRACTED: The Collective Effect of MIP-3α and FL Promotes Dendritic Cell Function Within the Immune Microenvironment of Murine Liver Cancer

Hepatic Dendritic Cells, the Tolerogenic Liver Environment, and Liver Disease

Dendritic Cell-Based Immunotherapy for Solid Tumors

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