Interleukin-7 Gene-Modified Dendritic Cells Reduce Pulmonary Tumor Burden in Spontaneous Murine Bronchoalveolar Cell Carcinoma

Sharma, Sherven; Batra, Raj K.; Yang, Seung Ho; Hillinger, Sven; Zhu, Li; Atianzar, Kimberly; Strieter, Robert M.; Riedl, Karen; Huang, Min; Dubinett, Steven M.

doi:10.1089/104303403322495025

Cited by 51 publications

(39 citation statements)

References 66 publications

(78 reference statements)

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“…In fact, injection of recombinant secondary lymphoid tissue chemokine in the axillary lymph node region in mice with bilateral multifocal pulmonary adenocarcinomas led to a marked reduction in tumor burden with extensive lymphocytic and DC infiltration of the tumors and enhanced survival (39). Together with clinical evidence demonstrating that infiltration of tumor mass by DC is associated with a better patient survival, these results suggest that regulated induction of DC migration into the tumor site might induce efficient antitumor immune responses.…”

Section: Discussionmentioning

confidence: 82%

Loss of New Chemokine CXCL14 in Tumor Tissue Is Associated with Low Infiltration by Dendritic Cells (DC), while Restoration of Human CXCL14 Expression in Tumor Cells Causes Attraction of DC Both In Vitro and In Vivo

Shurin¹,

Ferris

Tourkova³

et al. 2005

The Journal of Immunology

186

141

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Breast and kidney-expressed chemokine (BRAK) CXCL14 is a new CXC chemokine with unknown function and receptor selectivity. The majority of head and neck squamous cell carcinoma (HNSCC) and some cervical squamous cell carcinoma do not express CXCL14 mRNA, as opposed to constitutive expression by normal oral squamous epithelium. In this study, we demonstrate that the loss of CXCL14 in HNSCC cells and at HNSCC primary tumor sites was correlated with low or no attraction of dendritic cell (DC) in vitro, and decreased infiltration of HNSCC mass by DC at the tumor site in vivo. Next, we found that recombinant human CXCL14 and CXCL14-positive HNSCC cell lines induced DC attraction in vitro, whereas CXCL14-negative HNSCC cells did not chemoattract DC. Transduction of CXCL14-negative HNSCC cell lines with the human CXCL14 gene resulted in stimulation of DC attraction in vitro and increased tumor infiltration by DC in vivo in chimeric animal models. Furthermore, evaluating the biologic effect of CXCL14 on DC, we demonstrated that the addition of recombinant human CXCL14 to DC cultures resulted in up-regulation of the expression of DC maturation markers, as well as enhanced proliferation of allogeneic T cells in MLR. Activation of DC with recombinant human CXCL14 was accompanied by up-regulation of NF-κB activity. These data suggest that CXCL14 is a potent chemoattractant and activator of DC and might be involved in DC homing in vivo.

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Section: Discussionmentioning

confidence: 82%

Loss of New Chemokine CXCL14 in Tumor Tissue Is Associated with Low Infiltration by Dendritic Cells (DC), while Restoration of Human CXCL14 Expression in Tumor Cells Causes Attraction of DC Both In Vitro and In Vivo

Shurin¹,

Ferris

Tourkova³

et al. 2005

The Journal of Immunology

186

141

View full text Add to dashboard Cite

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“…14 In the case of IL-7, there is therapeutic evidence even in lung cancer arising in mice transgenic for an oncogene after being peritumorally injected with DCs engineered to produce IL-7. 29 In this regard, we have experimental evidence showing that intratumoral DCs transfected to produce IL-15 induce curative immunity in some mouse tumor models (data not shown). Even untransfected immature DCs when injected inside tumor tissue can induce systemic antitumor immunity that controls micrometastasis but not the primary tumor.…”

Section: Discussionmentioning

confidence: 94%

Dendritic cells delivered inside human carcinomas are sequestered by interleukin‐8

Feijoó

Alfaro

Mazzolini

et al. 2005

Intl Journal of Cancer

111

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In the course of a clinical trial consisting of intratumoral injections of dendritic cells (DCs) transfected to produce interleukin-12, the use of In-labeled tracing doses of DCs showed that most DCs remained inside tumor tissue, instead of migrating out. In search for factors that could explain this retention, it was found that tumors from patients suffering hepatocellular carcinoma, colorectal or pancreatic cancer were producing IL-8 and that this chemokine attracted monocyte-derived dendritic cells that uniformly express both IL-8 receptors CXCR1 and CXCR2. Accordingly, neutralizing antihuman IL-8 monoclonal antibodies blocked the chemotactic attraction of DCs by recombinant IL-8, as well as by the serum of the patients or culture supernatants of human colorectal carcinomas. In addition, tissue culture supernatants of colon carcinoma cells inhibited DC migration induced by MIP-3b in an IL-8-dependent fashion. IL-8 production in malignant tissue and the responsiveness of DCs to IL-8 are a likely explanation of the clinical images, which suggest retention of DCs inside human malignant lesions. Impairment of DC migration toward lymphoid tissue could be involved in cancer immune evasion. ' 2005 Wiley-Liss, Inc.

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“…33,34 Furthermore, intratumoral injection of DC transduced with CCL21 also led to systemic TH1-polarized anti-tumor immunity. 35,36 Qin et al 37 have recently demonstrated in a mouse tumor model for prostate cancer that immunogenicity of a multiepitope DNA vaccine encoding prostate-tumor-associated antigens can be enhanced by a CCL21/prostate antigenfusion gene.…”

Section: Discussionmentioning

confidence: 99%

CCL21 (SLC) improves tumor protection by a DNA vaccine in a Her2/neu mouse tumor model

et al. 2011

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Secondary lymphoid-tissue chemokine (SLC/CCL21) is a CC chemokine that is constitutively expressed in various lymphoid tissues and binds to chemokine receptor CCR7 on mature dendritic cells (DCs) and distinct T-and B-cell sub-populations. In vivo, CCL21 regulates the encounters between DC and T cells and thus is a key regulator of adaptive immune responses. We asked whether CCL21 is able to augment immunogenicity of a DNA-based vaccine against Her2/neu in a Balb/c mouse model with syngeneic Her2/neu þ tumor cells (D2F2/E2). Mice were vaccinated intramuscularly with plasmid DNA (pDNA) on day 1 and boosted on day 15; tumor challenge was performed subcutaneously on day 25. Coexpression of CCL21 and Her-2/neu resulted in induction of a TH1-polarized immune response and substantial improvement of the protective effect of the DNA vaccine. Coexpression of tumor antigen pDNA(Her2/neu) with both pDNA(GM-CSF) and pDNA(CCL21) as adjuvants led to further improvement of protection by the vaccine (70% tumor-free mice on day 35 vs 40% with either adjuvant alone vs 5-10% with tumor antigen alone). Our results show that CCL21 is a potent adjuvant for DNA vaccination, particularly in combination with granulocyte-macrophage colony-stimulating factor (GM-CSF). Clinical use of a pDNA(Her2/neu/CCL21/GM-CSF) vaccine might be particularly promising in minimal residual Her2/neu þ breast cancer.

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Interleukin-7 Gene-Modified Dendritic Cells Reduce Pulmonary Tumor Burden in Spontaneous Murine Bronchoalveolar Cell Carcinoma

Cited by 51 publications

References 66 publications

Loss of New Chemokine CXCL14 in Tumor Tissue Is Associated with Low Infiltration by Dendritic Cells (DC), while Restoration of Human CXCL14 Expression in Tumor Cells Causes Attraction of DC Both In Vitro and In Vivo

Loss of New Chemokine CXCL14 in Tumor Tissue Is Associated with Low Infiltration by Dendritic Cells (DC), while Restoration of Human CXCL14 Expression in Tumor Cells Causes Attraction of DC Both In Vitro and In Vivo

Dendritic cells delivered inside human carcinomas are sequestered by interleukin‐8

CCL21 (SLC) improves tumor protection by a DNA vaccine in a Her2/neu mouse tumor model

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