Dendritic cell based immunotherapy using tumor stem cells mediates potent antitumor immune responses

Dashti, Amir; Ebrahimi, Marzieh; Hadjati, Jamshid; Memarnejadian, Arash; Moazzeni, Seyed Mohammad

doi:10.1016/j.canlet.2016.01.021

Cited by 67 publications

(41 citation statements)

References 41 publications

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“…The impact of anticancer immunity partly depends on the function of T lymphocytes. This study showed that the vaccines played a crucial role in the development of DCs, CD8 + and CD4 + T cells in the immune response, which same with evaluation of effectiveness of DCs based vaccine against CSCs in other model [12].…”

Section: Discussionsupporting

confidence: 73%

Immunotherapy against metastatic bladder cancer by combined administration of granulocyte macrophage‐colony stimulating factor and interleukin‐2 surface modified MB49 bladder cancer stem cells vaccine

Wang¹,

Hua

Liu

et al. 2017

Cancer Medicine

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In previous studies, it has been shown that the granulocyte macrophage‐colony stimulating factor (GM‐CSF) or interleukin‐2 (IL‐2) surface modified MB49 bladder cancer stem cells (MCSCs) vaccine could induce a specific antitumor immunity and against bladder cancer in mice model respectively. However, whether combined administration of GM‐CSF and IL‐2 could produce specific immune responses to cancer stem cells (CSCs) was uncertain. MCSCs were established and characterized. GM‐CSF and IL‐2 MCSCs vaccines were prepared and bioactivity was evaluated. The therapeutic, protective, specific, and memorial immune response animal experiments were designed. Tumor‐specific cytotoxic T lymphocytes assay, enzyme linked immunosorbent assay, flow cytometry assay were performed to indentify whether vaccine caused an antitumor immunity. Streptavidin (SA)‐GM‐CSF and SA‐IL‐2 MCSCs vaccines were prepared successfully. Such vaccines inhibited the volume of tumor and prolonged the survival of the mice in animal experiments. The express of IgG or IFN‐c, the portion of dendritic cells, CD8+ and CD4+ T cells were highest in the combined vaccines group than the SA‐GM‐CSF vaccine group, the SA‐IL‐2 vaccine group, the MCSCs group and the PBS group. The combined of GM‐CSF and IL‐2 vaccines could induce better antitumor immunity than a vaccine alone.

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Section: Discussionsupporting

confidence: 73%

Immunotherapy against metastatic bladder cancer by combined administration of granulocyte macrophage‐colony stimulating factor and interleukin‐2 surface modified MB49 bladder cancer stem cells vaccine

Wang¹,

Hua

Liu

et al. 2017

Cancer Medicine

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“…They also observed increased NK cell and cytotoxic splenocyte activity against B16F10 cells, as well as a reduction in NY-ESO-1 antigen expression (high in B16F10-CSCs), in melanoma tumors formed in vivo. In another study, Dashti et al [27] used a DC vaccine pulsed with cell lysates of CSCs (CD24+CD44+), isolated from the B16F10 cell line in a prophylactic murine model. They demonstrated a significantly extended time to tumor take and prolonged OS.…”

Section: Discussionmentioning

confidence: 99%

Novel Genetic Melanoma Vaccines Based on Induced Pluripotent Stem Cells or Melanosphere-Derived Stem-Like Cells Display High Efficacy in a murine Tumor Rejection Model

Gąbka-Buszek

Kwiatkowska-Borowczyk

Jankowski

et al. 2020

Vaccines

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Therapeutic cancer vaccines have elicited renewed interest due to the development of immune checkpoint inhibitors. The role of these vaccines is to induce specific effector cells for killing cancer cells. Cancer stem cells (CSCs) are responsible for tumor growth and progression. Accordingly, they are targets for various cancer therapies, including immunotherapy. Here, we demonstrate the effectiveness of melanoma vaccines composed of genetically modified tumor cells admixed with melanoma stem-like cells (MSC) or induced pluripotent stem cells (iPSCs). Two vaccines were constructed. The first vaccine contained cells derived from B16F10 melanospheres (SFs) with CSC characteristics. The second vaccine contained syngeneic murine induced pluripotent stem cells (miPSCs). iPSCs or SF cells were admixed with B16F10 cells, modified with the designer cytokine Hyper-IL6(H6) (B16/H6). Control mice received B16/H6 cells, B16F10 cells or PBS. Immunization with either vaccine significantly inhibited tumor growth and increased disease-free survival (DFS) and overall survival (OS) in C57BL/6 mice. Mice treated with the SF or iPSC vaccine demonstrated increased activation of the immune response in the vaccination site and tumor microenvironment compared to those treated with B16/H6, B16F10 or PBS. Higher infiltration of dendritic cells (DCs) monocytes, and natural killer (NK) cells; lower numbers of myeloid-derived suppressor cells (MDSCs) and regulatory T cells (Tregs); higher levels of the cytokines INFγ and IL-12 were observed with the novel vaccines than with the control treatments. In vitro restimulation of splenocytes derived from mice immunized with B16F10 cell, SF cell or miPSC lysates increased the proliferation of CD4+ T helper lymphocytes and secretion of cytokines. An increased serum titer of antibodies directed against B16F10 cells was found in mice immunized with the SF vaccine. The most effective DFS and OS extensions were reached with the miPSCs vaccine. The described results form the basis for a novel platform for the next generation of cancer vaccines composed of allogeneic cancer-specific cells modified with a molecular adjuvant gene and admixed with allogeneic miPSCs or SFs.

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“…Currently, there have been many clinical trials of immunotherapeutic approaches targeting CSCs. For instance, CSC-DC vaccine, aiming to inhibit immune suppression induced by CSC, is under investigation [34].…”

Section: Discussionmentioning

confidence: 99%

CD44, A Marker of Cancer Stem Cells, is Positively Correlated With PD-L1 Expression and Immune Cells Infiltration in Lung Adenocarcinoma

Zhang

Wang

et al. 2020

Preprint

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Background: PD-L1 inhibitors is widely applied in lung adenocarcinoma patients. Tumor cells with high PD-L1 expression could trigger immune evasion. Cancer stem cells (CSCs) can evade from immunesurveillance due to their immunomodulating effects. However, the correlation between CSC and PD-L1 and some immune-related markers is seldom reported in patients with lung adenocarcinoma. Therefore, we aimed to ascertain their association in lung adenocarcinoma patients. Methods: We assessed CD44 expression and its association with PD-L1 in lung adenocarcinoma, using Tumor Immune Estimation Resource (TIMER), which was further validated in our patient cohort. The immune cells infiltration was depicted by CIBERSORT using GEO database. The correlation between CD44 and immune cells was also analyzed. We further evaluated the prognostic role of CD44 in patients with lung adenocarcinoma both using Kaplan-Meier plotter and validated in our patient cohort. Results: Positive association between CD44 and PD-L1 were found in lung adenocarcinoma patients. T cells CD4 memory resting cells and mast cells resting cells varied significantly between patients with CD44 high and those with CD44 low. Furthermore, positive association could be found between CD44 expression and immune cells. Arm-level depletion of CD44 was linked with B cell, CD4+ T cell, neutrophil and dendritic cell infiltration. Patients with higher CD44 levels had worsened overall survival (OS). Conclusions: In summary, these results demonstrate that CD44 was associated with PD-L1 and infiltration of immune cells, and was a negative prognostic factor for predicting worsened OS in lung adenocarcinoma.

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Dendritic cell based immunotherapy using tumor stem cells mediates potent antitumor immune responses

Cited by 67 publications

References 41 publications

Immunotherapy against metastatic bladder cancer by combined administration of granulocyte macrophage‐colony stimulating factor and interleukin‐2 surface modified MB49 bladder cancer stem cells vaccine

Immunotherapy against metastatic bladder cancer by combined administration of granulocyte macrophage‐colony stimulating factor and interleukin‐2 surface modified MB49 bladder cancer stem cells vaccine

Novel Genetic Melanoma Vaccines Based on Induced Pluripotent Stem Cells or Melanosphere-Derived Stem-Like Cells Display High Efficacy in a murine Tumor Rejection Model

CD44, A Marker of Cancer Stem Cells, is Positively Correlated With PD-L1 Expression and Immune Cells Infiltration in Lung Adenocarcinoma

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Dendritic cell based immunotherapy using tumor stem cells mediates potent antitumor immune responses

Cited by 67 publications

References 41 publications

Immunotherapy against metastatic bladder cancer by combined administration of granulocyte macrophage‐colony stimulating factor and interleukin‐2 surface modified MB49 bladder cancer stem cells vaccine

Immunotherapy against metastatic bladder cancer by combined administration of granulocyte macrophage‐colony stimulating factor and interleukin‐2 surface modified MB49 bladder cancer stem cells vaccine

Novel Genetic Melanoma Vaccines Based on Induced Pluripotent Stem Cells or Melanosphere-Derived Stem-Like Cells Display High Efficacy in a murine Tumor Rejection Model

CD44, A Marker of Cancer Stem Cells, is Positively Correlated With PD-L1&nbsp;Expression and Immune Cells Infiltration in Lung Adenocarcinoma

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CD44, A Marker of Cancer Stem Cells, is Positively Correlated With PD-L1 Expression and Immune Cells Infiltration in Lung Adenocarcinoma