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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.
This article was published in the following journal.
Name: Nature communications
Tumor cells benefit from tumor-associated macrophages (TAMs) promoting tumor growth and modulating functions of other cells in tumor microenvironment (TME). However, how tumor cells regulate the prope...
FOXP3 is a transcription factor, which belongs to the family of FOX protein. FOXP3 was initially discovered in regulatory T cells and supposed to play a significant role in the process of regulatory T...
Whole tumor cell lysates consist of a mixture of tumor antigens and danger associated molecular patterns (DAMPs) that can be used for dendritic cell maturation and consequently for the activation of a...
Anti- tumor vaccination elicits imperfect immune responses against tumor cells; that is related to the presence of suppressive obstacles in the tumor microenvironment. The main members of suppressive ...
Dendritic cells are a specialized type of antigen-presenting cell that bridges both innate and adaptive immune system function. While much is understood about dendritic cells and their role in the imm...
The aim of the study is to show if vaccination with autologous dendritic cells pulsed with peptides or tumor lysate in combination with adjuvant cytokines and Cyclophosphamide can induce a...
RATIONALE: Vaccines made from a patient's white blood cells (dendritic cells) and a specific leukemia antigen (Wilms tumor antigen-1) may induce an effective immune response to kill residu...
This study investigates the use of the patients own immune cells to treat prostate cancer. Cells are taken from the patient and grown in the laboratory to become specialized immune cells c...
The purpose of this study is to show if vaccination with autologous dendritic cells pulsed with peptides or tumor lysate in combination with adjuvant cytokines can induce a measurable immu...
This study is being conducted to determine the efficacy, side effects, and toxicity of an investigational vaccine that consists of tumor-pulsed dendritic cells administered with an immune ...
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.
The pancreas secretes a number of important hormones into the digestive tract and the blood stream. Cancers are most commonly exocrine than endocrine (neuroendocrine) tumors. Functional tumors secrete hormones; Insulinoma, Gastrinoma, Somatostatinoma, VI...
Allergies Automimmune Disease Human Papillomavirus (HPV) Immunology Vaccine Immunology is the study of immunity and the defence mechanisms of the body. A greater understanding of immunology is needed to develop vaccines, understand ...