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Specialized dendritic cells induce tumor-promoting IL-10IL-17 FoxP3 regulatory CD4 T cells in pancreatic carcinoma.

08:00 EDT 29th March 2019 | BioPortfolio

Summary of "Specialized dendritic cells induce tumor-promoting IL-10IL-17 FoxP3 regulatory CD4 T cells in pancreatic carcinoma."

The drivers and the specification of CD4 T cell differentiation in the tumor microenvironment and their contributions to tumor immunity or tolerance are incompletely understood. Using models of pancreatic ductal adenocarcinoma (PDA), we show that a distinct subset of tumor-infiltrating dendritic cells (DC) promotes PDA growth by directing a unique T-program. Specifically, CD11bCD103 DC predominate in PDA, express high IL-23 and TGF-β, and induce FoxP3 tumor-promoting IL-10IL-17IFNγregulatory CD4 T cells. The balance between this distinctive T program and canonical FoxP3T is unaffected by pattern recognition receptor ligation and is modulated by DC expression of retinoic acid. This T-signature is mimicked in human PDA where it is associated with immune-tolerance and diminished patient survival. Our data suggest that CD11bCD103 DC promote CD4 T cell tolerance in PDA which may underscore its resistance to immunotherapy.

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This article was published in the following journal.

Name: Nature communications
ISSN: 2041-1723
Pages: 1424

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Medical and Biotech [MESH] Definitions

Non-hematopoietic cells, with extensive dendritic processes, found in the primary and secondary follicles of lymphoid tissue (the B cell zones). They are different from conventional DENDRITIC CELLS associated with T-CELLS. They are derived from MESENCHYMAL STEM CELLS and are negative for class II MHC antigen and do not process or present antigen like the conventional dendritic cells do. Instead, follicular dendritic cells have FC RECEPTORS and C3B RECEPTORS that hold antigen in the form of ANTIGEN-ANTIBODY COMPLEXES on their surfaces for long periods for recognition by B-CELLS.

Recirculating, dendritic, antigen-presenting cells containing characteristic racket-shaped granules (Birbeck granules). They are found principally in the stratum spinosum of the EPIDERMIS and are rich in Class II MAJOR HISTOCOMPATIBILITY COMPLEX molecules. Langerhans cells were the first dendritic cell to be described and have been a model of study for other dendritic cells (DCs), especially other migrating DCs such as dermal DCs and INTERSTITIAL DENDRITIC CELLS.

Specialized cells of the hematopoietic system that have branch-like extensions. They are found throughout the lymphatic system, and in non-lymphoid tissues such as SKIN and the epithelia of the intestinal, respiratory, and reproductive tracts. They trap and process ANTIGENS, and present them to T-CELLS, thereby stimulating CELL-MEDIATED IMMUNITY. They are different from the non-hematopoietic FOLLICULAR DENDRITIC CELLS, which have a similar morphology and immune system function, but with respect to humoral immunity (ANTIBODY PRODUCTION).

A family of proteins that were originally identified by their ability to cause NECROSIS of NEOPLASMS. Their necrotic effect on cells is mediated through TUMOR NECROSIS FACTOR RECEPTORS which induce APOPTOSIS.

A CC-type chemokine highly expressed in the lungs, lymph nodes, placenta, and bone marrow; it is also expressed by DENDRITIC CELLS in the GERMINAL CENTER, and peripheral blood MACROPHAGES. It functions as a chemotactic factor that specifically attracts LYMPHOCYTES, especially B-Cells, into lymph node follicles, and naive T-cells towards dendritic cells and activated T-cells. It does not attract MONOCYTES or GRANULOCYTES.

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