Phenotypic Characterisation of the Dendritic Cell Infiltrate in Prostate Cancer

Troy, Andrew; Davidson, Peter; Ch, Atkinson; Hart, Derek N. J.

doi:10.1097/00005392-199807000-00087

Cited by 21 publications

(22 citation statements)

References 16 publications

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“…This has now been studied in several human cancers. Immunohistological analysis of renal cell carcinoma suggested that DCs were present in normal numbers in the malignant tissue and no evidence of increased activation was found [59]. Similar findings were made in prostate cancer [60], and by us [61] and others [62] in breast cancer.…”

Section: In Human Cancersupporting

confidence: 85%

Dendritic Cells and Cancer: Prospects for Cancer Vaccination

Hart

Jackson²,

Nestle³

2002

Cancer Immune Therapy

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Effective therapeutic cancer vaccination is an old dream, now rekindled by modern advances in cell biology and immunology. Several key facts have inspired the current optimism for clinical immunotherapy trials. First, the realization that, by definition, every malignant cell must express at least one gene product in an abnormal fashion means that theoretically there is at least one tumor-associated antigen (TAA) (it may be an autoantigen) available as a target. Secondly, we now know that any cellular protein (membrane, cytoplasmic or nuclear) may be presented as a peptide, in the context of major histocompatibility complex (MHC) molecules, for recognition by the T lymphocyte receptor complex. Thirdly, whilst it is clear that the immune response has failed the cancer patient, it is also true that it has not suffered irreversible meltdown, i. e. deletion of tumor-reactive T lymphocytes. Finally, it is now recognized that dendritic cells (DCs) are the key cellular elements for initiating and directing immune responses. As DC biology appears to be abnormal in cancer patients, the simplest hypothesis of the day is to use activated DCs to present relevant TAAs to the patient's immune system and thus generate an effective therapeutic response. This chapter will review the physiology of DC biology in the cancer patient, DC preparations and clinical trial results, whilst predicting areas requiring attention in order to optimize DC cancer vaccination for future patient benefit. DC PropertiesDCs originate from CD34 + hematopoietic stem cells, circulate in peripheral blood and are found in virtually all tissues of the body. In peripheral blood, DCs are a morphologically heterogeneous cell population, including DCs with membrane processes (ªmyeloid DCº) and DCs with plasmacytoid morphology (ªplasmacytoid monocytesº, ªplasmacytoid T lymphocyteº, ªlymphoid DCsº) [1,2]. In the skin, DCs are present as epidermal Langerhans cells (LCs) with their characteristic Birbeck ISBNs: 3-527-30441-X (Hardback);(Electronic) 3-527-60079-5 granules [3] and dermal DCs [4,5], which have a subtly different morphology and phenotype. In secondary lymphoid tissues they are present as interdigitating DCs with prominent membrane processes in the T cell area and as ªplasmacytoid monocytesº around high endothelial venules (HEVs) [6]. Monocytes may also differentiate directly into DC-like cells in sites of inflammation [7]. Whilst there is some uncertainty about the identity of the different DC populations and their differentiation, it is clear that a variety of growth factors and cytokines drive DC development [8]. Furthermore, chemokines direct their migration [9] and other soluble compounds influence their function.Blood DCs are commonly defined as lineage negative (Lin ± ), MHC class II positive (MHC-II + ) cells, lacking the CD14 (monocyte), CD3 (T cell), CD19 (B cell) and CD56 [natural killer (NK) cell] lineage markers, but expressing MHC class II molecules at high density, on their surface. They express various adhesion molecules including CD11 a ...

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Section: In Human Cancersupporting

confidence: 85%

Dendritic Cells and Cancer: Prospects for Cancer Vaccination

Hart

Jackson²,

Nestle³

2002

Cancer Immune Therapy

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“…DCs isolated from mouse and human tumors have been shown to be resistant to a variety of maturation signals in vitro ; however, this block in maturation can be readily reversed by the addition of anti‐IL‐10 antibodies to culture conditions (163, 217, 218). Interestingly, these immature DCs tended to be more tolerogenic than immunogenic APCs with decreased production of IL‐12 and TNF‐α and increased secretion of IL‐10 and TGF‐β (199, 219–222). Recently, the role of DC‐derived IL‐10 in DC‐based tumor immunology was investigated employing DCs derived from IL‐10‐deficient mice.…”

Section: Antagonism Of Il‐10 In Promoting Anti‐tumor Immunitymentioning

confidence: 99%

Strategies for use of IL‐10 or its antagonists in human disease

O’Garra¹,

Barrat

Castro

et al. 2008

Immunological Reviews

394

310

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Summary: Interleukin‐10 (IL‐10) is a cytokine with broad anti‐inflammatory properties by its suppression of both macrophage and dendritic cell function, including antigen‐presenting cell function and the production of proinflammatory cytokines. This can result subsequently in the feedback regulation of both T‐helper 1 (Th1)‐type and Th2‐type responses. This review discusses the potential use of IL‐10 or agents that induce IL‐10 as potential anti‐inflammatory therapies in inflammatory diseases. Although IL‐10‐deficient mice develop colitis in the presence of normal gut flora and clear certain intracellular pathogens more efficiently, this is often accompanied by immunopathology, which can be lethal to the host. This reinforces the anti‐inflammatory properties of IL‐10, although it should be noted that as discussed below, IL‐10 can also promote B‐cell and other immune responses under particular settings. A penalty of its role to limit the immune and inflammatory responses to pathogens and prevent damage to the host is that high or dysregulated levels of IL‐10 may result in chronic infection. Thus, antagonists of IL‐10 show great potential as adjuvants in preventative or therapeutic vaccines against chronic infection or cancer. This article reviews basic published studies on IL‐10, which may lead to potential uses of IL‐10 or its antagonists in human disease.

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“…[1][2][3][4] DC activate both naive and memory CD4 ϩ and CD8 ϩ T cells [35][36][37] and seem to meet all requirements as a strong immune-activator for anti-tumor immunity or immunity against microbial infection. [38][39][40] Located in most host tissues, DC function as immune sentinels for infectious agents and inflammatory products of bacteria. Immature DC can capture antigens in peripheral tissues and undergo maturation processes to stimulate naive T cells in secondary lymphoid organs.…”

Section: Pl Is Involved With Erk P38 Kinases and Nf-k Kb P65mentioning

confidence: 99%