Dendritic cell plasticity in tumor-conditioned skin: CD14+ cells at the cross-roads of immune activation and suppression
Tumors abuse myeloid plasticity to re-direct dendritic cell (DC) differentiation from T cell stimulatory subsets to immune suppressive subsets that can interfere with antitumor immunity. Lined by a dense network of easily accessible DC the skin is a preferred site for the delivery of DC-targeted vac...
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doaj-ee82493151874306abafa72f4737dcc42020-11-24T23:04:30ZengFrontiers Media S.A.Frontiers in Immunology1664-32242013-11-01410.3389/fimmu.2013.0040370009Dendritic cell plasticity in tumor-conditioned skin: CD14+ cells at the cross-roads of immune activation and suppressionRieneke evan de Ven0Rieneke evan de Ven1Jelle Jan Lindenberg2Dinja eOosterhoff3Tanja Denise De Gruijl4VU University medical centerEarle A. Chiles Research Institute, Providence Cancer CenterVU University medical centerVU University medical centerVU University medical centerTumors abuse myeloid plasticity to re-direct dendritic cell (DC) differentiation from T cell stimulatory subsets to immune suppressive subsets that can interfere with antitumor 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.http://journal.frontiersin.org/Journal/10.3389/fimmu.2013.00403/fullDendritic CellsMacrophagesSkinCancerimmune suppressionhuman DC subsets |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Rieneke evan de Ven Rieneke evan de Ven Jelle Jan Lindenberg Dinja eOosterhoff Tanja Denise De Gruijl |
spellingShingle |
Rieneke evan de Ven Rieneke evan de Ven Jelle Jan Lindenberg Dinja eOosterhoff Tanja Denise De Gruijl Dendritic cell plasticity in tumor-conditioned skin: CD14+ cells at the cross-roads of immune activation and suppression Frontiers in Immunology Dendritic Cells Macrophages Skin Cancer immune suppression human DC subsets |
author_facet |
Rieneke evan de Ven Rieneke evan de Ven Jelle Jan Lindenberg Dinja eOosterhoff Tanja Denise De Gruijl |
author_sort |
Rieneke evan de Ven |
title |
Dendritic cell plasticity in tumor-conditioned skin: CD14+ cells at the cross-roads of immune activation and suppression |
title_short |
Dendritic cell plasticity in tumor-conditioned skin: CD14+ cells at the cross-roads of immune activation and suppression |
title_full |
Dendritic cell plasticity in tumor-conditioned skin: CD14+ cells at the cross-roads of immune activation and suppression |
title_fullStr |
Dendritic cell plasticity in tumor-conditioned skin: CD14+ cells at the cross-roads of immune activation and suppression |
title_full_unstemmed |
Dendritic cell plasticity in tumor-conditioned skin: CD14+ cells at the cross-roads of immune activation and suppression |
title_sort |
dendritic cell plasticity in tumor-conditioned skin: cd14+ cells at the cross-roads of immune activation and suppression |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Immunology |
issn |
1664-3224 |
publishDate |
2013-11-01 |
description |
Tumors abuse myeloid plasticity to re-direct dendritic cell (DC) differentiation from T cell stimulatory subsets to immune suppressive subsets that can interfere with antitumor 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. |
topic |
Dendritic Cells Macrophages Skin Cancer immune suppression human DC subsets |
url |
http://journal.frontiersin.org/Journal/10.3389/fimmu.2013.00403/full |
work_keys_str_mv |
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