Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
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Target Concepts:
Gene/Protein
Disease
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Enzyme
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Query: UNIPROT:P06126 (
CD1a
)
2,221
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
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.
...
PMID:Functional characterization of a STAT3-dependent dendritic cell-derived CD14
+
cell population arising upon IL-10-driven maturation. 2373 30
Natural polyphenolic compounds of grapes and their seeds are thought to be therapeutic adjuvants in a variety of diseases, including cancer prevention. This study was carried out to investigate the effect of grape phenolic compounds on the regulation of cancer-mediated immune suppression. Laricitrin exhibits the greatest potential to ameliorate the suppressive effects of lung cancer on dendritic cells' (DCs') differentiation, maturation and function. Human lung cancer A549 and CL1-5 cells change the phenotype of DCs that express to high levels of IL-10 and prime T cells towards an immune suppression type-2 response (Th2). Laricitrin treatment stimulated DC differentiation and maturation in the condition media of cancer cells, a finding supported by monocyte marker CD14's disappearance and DC marker
CD1a
's upregulation. Laricitrin decreases expression of IL-10 in cancer-conditioned DCs, and subsequently switches CD4+ T cell response from Th2 to Th1 in vitro and in vivo. Reversal of laricitrin on lung cancer-induced DCs' paralysis was via inhibiting the phosphorylation of
signal transducer and activator of transcription 3
(
STAT3
). Laricitrin also potentiated the anticancer activity of cisplatin in mouse models. Thus, laricitrin could be an efficacious immunoadjuvant and have a synergistic effect when combined with chemotherapy.
...
PMID:Laricitrin ameliorates lung cancer-mediated dendritic cell suppression by inhibiting signal transducer and activator of transcription 3. 2783 81
