Dendritic Cells (DC) Facilitate Detachment of Squamous Carcinoma Cells (SCC), While SCC Promote an Immature CD16+ DC Phenotype and Control DC Migration

Ramanathapuram, Lalitha; Hopkin, Dustin; Kurago, Zoya B.

doi:10.1007/s12307-011-0077-4

Cited by 12 publications

(9 citation statements)

References 49 publications

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“…We and others have found evidence of phenotypically similar subsets in breast, colon, head and neck, renal cell, and melanoma tumors (17, 37–39). Indeed, in single-cell suspensions derived from a panel of six metastatic melanoma tumors, we observed by multicolor flow cytometry analysis, that CD14 + cells, co-expressing both DC-SIGN and BDCA3 and detectable in a range of 1–38%, significantly outnumbered CD1a + DC, which were virtually absent (ranging from 0.05 to 0.1%) (17).…”

Section: Tumors Abuse DC Plasticity To Undermine Immunity: a Central supporting

confidence: 55%

“…From our observations we conclude that combined expression of CD14, BDCA3, DC-SIGN, CD16, and CD163 provides a phenotypic profile useful for the identification of M2-macrophage-like subsets with immune-suppressive and tumor-promoting characteristics that arise during tumor-conditioned differentiation or maturation of human DCs. We and others have found evidence of phenotypically similar subsets in breast, colon, head and neck, renal cell, and melanoma tumors ( 17 , 37 – 39 ). Indeed, in single-cell suspensions derived from a panel of six metastatic melanoma tumors, we observed by multicolor flow cytometry analysis, that CD14 + cells, co-expressing both DC-SIGN and BDCA3 and detectable in a range of 1–38%, significantly outnumbered CD1a + DC, which were virtually absent (ranging from 0.05 to 0.1%) ( 17 ).…”

Section: Tumors Abuse DC Plasticity To Undermine Immunity: a Central supporting

confidence: 55%

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Dendritic Cell Plasticity in Tumor-Conditioned Skin: CD14+ Cells at the Cross-Roads of Immune Activation and Suppression

et al. 2013

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Tumors abuse myeloid plasticity to re-direct dendritic cell (DC) differentiation from T cell stimulatory subsets to immune-suppressive subsets that can interfere with anti-tumor immunity. Lined by a dense network of easily accessible DC the skin is a preferred site for the delivery of DC-targeted vaccines. Various groups have recently been focusing on functional aspects of DC subsets in the skin and how these may be affected by tumor-derived suppressive factors. IL-6, Prostaglandin-E2, and IL-10 were identified as factors in cultures of primary human tumors responsible for the inhibited development and activation of skin DC as well as monocyte-derived DC. IL-10 was found to be uniquely able to convert fully developed DC to immature macrophage-like cells with functional M2 characteristics in a physiologically highly relevant skin explant model in which the phenotypic and functional traits of “crawl-out” DC were studied. Mostly from mouse studies, the JAK2/STAT3 signaling pathway has emerged as a “master switch” of tumor-induced immune suppression. Our lab has additionally identified p38-MAPK as an important signaling element in human DC suppression, and recently validated it as such in ex vivo cultures of single-cell suspensions from melanoma metastases. Through the identification of molecular mechanisms and signaling events that drive myeloid immune suppression in human tumors, more effective DC-targeted cancer vaccines may be designed.

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Section: Tumors Abuse DC Plasticity To Undermine Immunity: a Central supporting

confidence: 55%

Section: Tumors Abuse DC Plasticity To Undermine Immunity: a Central supporting

confidence: 55%

Dendritic Cell Plasticity in Tumor-Conditioned Skin: CD14+ Cells at the Cross-Roads of Immune Activation and Suppression

et al. 2013

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“…Rather, the combined expression of CD14, BDCA3, DC-SIGN, CD163 and CD16 appears to provide a phenotypic profile that would be useful for the identification of macrophage-like cell subsets that arise in the course of tumor-conditioned myeloid cell differentiation or maturation. We and others have identified such cell subsets in breast, colon, head and neck and melanoma lesions 24 , 37 . A phenotypically distinct human BDCA3 + DC subset found in the blood and the spleen efficiently cross-presents soluble or cell-associated antigens to CD8 + T cells 15 - 17 , 38 .…”

Section: Discussionmentioning

confidence: 93%

Functional characterization of a STAT3-dependent dendritic cell-derived CD14⁺cell population arising upon IL-10-driven maturation

et al. 2013

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Interleukin (IL)-10 is a major cancer-related immunosuppressive factor, exhibiting a unique ability to hamper the maturation of dendritic cells (DCs). We have previously reported that IL-10 induces the conversion of activated, migratory CD1a+ DCs found in the human skin to CD14+CD141+ macrophage-like cells. Here, as a model of tumor-conditioned DC maturation, we functionally assessed CD14- and CD14+ DCs that matured in vitro upon exposure to IL-10. IL-10-induced CD14+ DCs were phenotypically characterized by a low maturation state as well as by high levels of BDCA3 and DC-SIGN, and as such they closely resembled CD14+ cells infiltrating melanoma metastases. Compared with DC matured under standard conditions, CD14+ DCs were found to express high levels of B7-H1 on the cell surface, to secrete low levels of IL-12p70, to preferentially induce TH2 cells, to have a lower allogeneic TH cell and tumor antigen-specific CD8+ T-cell priming capacity and to induce proliferative T-cell anergy. In contrast to their CD14+ counterparts, CD14- monocyte-derived DCs retained allogeneic TH priming capacity but induced a functionally anergic state as they completely abolished the release of effector cytokines. Transcriptional and cytokine release profiling studies indicated a more profound angiogenic and pro-invasive signature of CD14+ DCs as compared with DCs matured in standard conditions or CD14− DCs matured in the presence of IL-10. Importantly, signal transducer and activator of transcription 3 (STAT3) depletion by RNA interference prevented the development of the IL-10-associated CD14+ phenotype, allowing for normal DC maturation and providing a potential means of therapeutic intervention.

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“…IFN-γ can increase tumor cell class I MHC expression and sensitivity to lysis by NK cells and cytotoxic T lymphocytes (CTLs). Besides, antigen-presenting cells such as macrophages and dendritic cells can directly activate antigen-specific Th1 or CTLs, which can activate the anti-tumor immune response and are thus associated with favorable prognosis in a diverse range of cancers ( 37 , 38 ).…”

Section: Discussionmentioning

confidence: 99%

Pathological Significance and Prognostic Value of Surfactant Protein D in Cancer

et al. 2018

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Surfactant protein D (SP-D) is a pattern recognition molecule belonging to the Collectin (collagen-containing C-type lectin) family that has pulmonary as well as extra-pulmonary existence. In the lungs, it is a well-established opsonin that can agglutinate a range of microbes, and enhance their clearance via phagocytosis and super-oxidative burst. It can interfere with allergen–IgE interaction and suppress basophil and mast cell activation. However, it is now becoming evident that SP-D is likely to be an innate immune surveillance molecule against tumor development. SP-D has been shown to induce apoptosis in sensitized eosinophils derived from allergic patients and a leukemic cell line via p53 pathway. Recently, SP-D has been shown to suppress lung cancer progression via interference with the epidermal growth factor signaling. In addition, a truncated form of recombinant human SP-D has been reported to induce apoptosis in pancreatic adenocarcinoma via Fas-mediated pathway in a p53-independent manner. To further establish a correlation between SP-D presence/levels and normal and cancer tissues, we performed a bioinformatics analysis, using Oncomine dataset and the survival analysis platforms Kaplan–Meier plotter, to assess if SP-D can serve as a potential prognostic marker for human lung cancer, in addition to human gastric, breast, and ovarian cancers. We also analyzed immunohistochemically the presence of SP-D in normal and tumor human tissues. We conclude that (1) in the lung, gastric, and breast cancers, there is a lower expression of SP-D than normal tissues; (2) in ovarian cancer, there is a higher expression of SP-D than normal tissue; and (3) in lung cancer, the presence of SP-D could be associated with a favorable prognosis. On the contrary, at non-pulmonary sites such as gastric, breast, and ovarian cancers, the presence of SP-D could be associated with unfavorable prognosis. Correlation between the levels of SP-D and overall survival requires further investigation. Our analysis involves a large number of dataset; therefore, any trend observed is reliable. Despite apparent complexity within the results, it is evident that cancer tissues that produce less levels of SP-D compared to their normal tissue counterparts are probably less susceptible to SP-D-mediated immune surveillance mechanisms via infiltrating immune cells.

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Dendritic Cells (DC) Facilitate Detachment of Squamous Carcinoma Cells (SCC), While SCC Promote an Immature CD16+ DC Phenotype and Control DC Migration

Cited by 12 publications

References 49 publications

Dendritic Cell Plasticity in Tumor-Conditioned Skin: CD14+ Cells at the Cross-Roads of Immune Activation and Suppression

Dendritic Cell Plasticity in Tumor-Conditioned Skin: CD14+ Cells at the Cross-Roads of Immune Activation and Suppression

Functional characterization of a STAT3-dependent dendritic cell-derived CD14⁺cell population arising upon IL-10-driven maturation

Pathological Significance and Prognostic Value of Surfactant Protein D in Cancer

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Dendritic Cells (DC) Facilitate Detachment of Squamous Carcinoma Cells (SCC), While SCC Promote an Immature CD16+ DC Phenotype and Control DC Migration

Cited by 12 publications

References 49 publications

Dendritic Cell Plasticity in Tumor-Conditioned Skin: CD14+ Cells at the Cross-Roads of Immune Activation and Suppression

Dendritic Cell Plasticity in Tumor-Conditioned Skin: CD14+ Cells at the Cross-Roads of Immune Activation and Suppression

Functional characterization of a STAT3-dependent dendritic cell-derived CD14+cell population arising upon IL-10-driven maturation

Pathological Significance and Prognostic Value of Surfactant Protein D in Cancer

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Product

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Functional characterization of a STAT3-dependent dendritic cell-derived CD14⁺cell population arising upon IL-10-driven maturation