IL-12/IL-18-Dependent IFN-γ Release by Murine Dendritic Cells

Stober, Detlef; Schirmbeck, Reinhold; Reimann, Jörg

doi:10.4049/jimmunol.167.2.957

Cited by 118 publications

(102 citation statements)

References 60 publications

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“…21 To investigate whether RT/IL-12 can enhance the maturation status of tumor-infiltrating myeloid cells, especially DCs, we analyzed the expression of three classic maturation markers, MHC class II, CD40 and CD86, in the different treatment groups. Figure 5(a) shows a representative histogram; the summarized results are shown in Figure 5(b).…”

Section: Resultsmentioning

confidence: 99%

Combination of radiation and interleukin 12 eradicates large orthotopic hepatocellular carcinoma through immunomodulation of tumor microenvironment

Tsai

Lee

et al. 2018

OncoImmunology

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Immunotherapies have shown promising results in certain cancer patients. For hepatocellular carcinoma (HCC), the multiplicity of an immunotolerant microenvironment within both the tumor, and the liver per se may limit the efficacy of cancer immunotherapies. Since radiation induces immunogenic cell death and inflammatory reactions within the tumor microenvironment, we hypothesized that a combination therapy of radiation and lasting local immunostimulating agents, achieved by intratumoral injection of an adenoviral vector encoding interleukin 12, may reverse the immunotolerant microenvironment within a well-established orthotopic HCC toward a state favorable for inducing antitumor immunities. Our data showed that radiation and IL-12 combination therapy (RT/IL-12) led to dramatic tumor regression in animals bearing large subcutaneous or orthotopic HCC, induced systemic effect against distant tumor, and significantly prolonged survival. Radiation monotherapy induced tumor regression at early times but afterwards most tumors regained exponential growth, while IL-12 monotherapy only delayed tumor growth. Mechanistic studies revealed that RT/IL-12 increased expression of MHC class II and co-stimulatory molecules CD40 and CD86 on tumor-infiltrating dendritic cells, suggesting an improvement of their antigen presentation activity. RT/IL-12 also significantly reduced accumulation of tumor-infiltrating myeloid-derived suppressor cells (MDSCs) and impaired their suppressive functions by reducing production of reactive oxygen species. Accordingly, tumor-infiltrating CD8+ T cells and NK cells were significantly activated toward the antitumor phenotype, as revealed by increased expression of CD107a and TNF-α. Together, our data showed that RT/IL-12 treatment could reset the intratumoral immunotolerant state and stimulate activation of antitumor cellular immunity that is capable of eliminating large established HCC tumors.

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Section: Resultsmentioning

confidence: 99%

Combination of radiation and interleukin 12 eradicates large orthotopic hepatocellular carcinoma through immunomodulation of tumor microenvironment

Tsai

Lee

et al. 2018

OncoImmunology

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“…In this context, spleen cells from CpG-treated donors could not transfer protection to IFN-c receptor KO mice (Table 2), since recipient cells were unresponsive to donor-derived IFNc. Previous studies showed that DC can produce IFN-c, although whether such cells express Thy1.2 was not examined [21][22][23][24][25][26]. As shown in Fig.…”

Section: Discussionmentioning

confidence: 99%

CpG-activated Thy1.2+ dendritic cells protect against lethalListeria monocytogenes infection

et al. 2005

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Synthetic oligodeoxynucleotides containing CpG motifs (CpG ODN) activate the innate immune system by interacting with Toll-like receptor 9. The resultant immune response increases host resistance to infection by a variety of pathogenic microorganisms, including Listeria monocytogenes. There is a considerable interest in harnessing the immunoprotective properties of CpG ODN, yet little is known of the cell phenotype(s) responsible for mediating this protection. This work demonstrates that treatment of mice with CpG ODN increases the number of Thy1.2 + , CD11c + dendritic cells (Thy1.2 + DC) in the spleen, which are both necessary and sufficient for transferring resistance to infection from CpG-treated donors to naive recipients. These CpG-activated Thy1.2 + DC are distinct from conventional (CD11c hi , Thy1.2 -) or plasmacytoid DC (mPDCA + ), and secrete IFN-c that contributes to protection. These findings suggest that a novel Thy1.2 + DC subset plays a critical role in mediating the immunoprotective activity of CpG DNA.

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“…Forty hours later, culture supernatants were collected for measurements of released IL-12 and IFN-␣ using standard ELISA. 14,15 …”

Section: Stimulated Cytokine Responsementioning

confidence: 99%

Cognate interactions between memory T cells and tumor antigen‐presenting dendritic cells from bone marrow of breast cancer patients: Bidirectional cell stimulation, survival and antitumor activity in vivo

Bai

Beckhove

Feuerer

et al. 2002

Intl Journal of Cancer

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IL-12/IL-18-Dependent IFN-γ Release by Murine Dendritic Cells

Cited by 118 publications

References 60 publications

Combination of radiation and interleukin 12 eradicates large orthotopic hepatocellular carcinoma through immunomodulation of tumor microenvironment

Combination of radiation and interleukin 12 eradicates large orthotopic hepatocellular carcinoma through immunomodulation of tumor microenvironment

CpG-activated Thy1.2+ dendritic cells protect against lethalListeria monocytogenes infection

Cognate interactions between memory T cells and tumor antigen‐presenting dendritic cells from bone marrow of breast cancer patients: Bidirectional cell stimulation, survival and antitumor activity in vivo

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