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Cutaneous T Cell Lymphoma (cutaneous t + cell_lymphoma)
Selected Abstracts,Activation-induced cell death': a special program able to preserve the homeostasis of the skin?EXPERIMENTAL DERMATOLOGY, Issue 1 2002Giuseppe De Panfilis Abstract: The ,activation-induced cell death' (AICD) is a molecular system leading to death of antigen-activated T lymphocytes, in order to avoid accumulation of harmful cytokine-releasing cells. This article reviews both the molecular mechanisms working in AICD and the role played by such mechanisms in preventing a number of skin diseases. Specifically, because AICD removes activated and autoreactive T cells through a CD95-/CD95-L-mediated suicide, skin diseases were scrutinized in which such valuable machinery could be lacking. Indeed, at least some inflammatory skin diseases, including psoriasis and atopic dermatitis, can be sustained by an increased survival of activated T lymphocytes associated with deficient CD95-/CD95-L-mediated AICD of such strong pro-inflammatory cells. In addition, autoreactive skin diseases, including, e.g. alopecia areata, lichen planus and other lichenoid tissue reactions, can be related to autoreactive T lymphocytes which could be unable to undergo CD95-/CD95-L-mediated AICD. Finally, a lack of AICD may be executive even in favoring cutaneous T cell lymphoma. Thus, because inflammatory, autoreactive and neoplastic skin diseases can be associated with a deficient CD95-/CD95-L-mediated suicide of activated T cells, AICD is likely to represent a fundamental program to preserve the homeostasis of the skin. Therapeutic approaches able to restore the AICD machinery promise to successfully treat such relevant skin diseases. [source] Extracorporeal photopheresis reduces the number of mononuclear cells that produce pro-inflammatory cytokines, when tested ex-vivoJOURNAL OF CLINICAL APHERESIS, Issue 4 2002John Bladon Abstract Extracorporeal photopheresis (ECP) has been shown to be clinically effective in the treatment of many T cell,mediated conditions. ECP's mechanism of action includes the induction of apoptosis and the release of pro-inflammatory cytokines. Recently, we have observed early lymphoid apoptosis, detectable immediately post ECP. We were interested to determine what influence ECP has on pro-inflammatory cytokine secretion at this early pre-infusion stage. Samples from 6 cutaneous T cell lymphoma (CTCL) and 5 graft versus host disease (GvHD) patients were taken pre ECP and immediately post ECP, prior to re-infusion. Following separation, the PBMCs were added to a cell culture medium and stimulated with PMA, Ionomycin, and Brefeldin A for 6 hours. Using flow cytometry, intracellular cytokine expression of IFN, and TNF, was determined in the T cell population. The monocytes were evaluated for IL6, IFN,, IL12, and TNF,. For both patient groups, the number of IFN,-expressing T cells fell significantly at re-infusion, whilst both T cell- and monocyte-expressing TNF, levels were reduced at re-infusion. All other cytokines tested showed no significant change post ECP. For GvHD, pro-inflammatory cytokines have a pathological role. Their down-regulation may have a direct clinical benefit. However, the reduction in the number of IFN,- and TNF,-expressing mononuclear cells means, at this early stage, it is unlikely that these cytokines assist in the removal of the malignant Th2 cells present in CTCL. J. Clin. Apheresis 17:177,182, 2002. © 2002 Wiley-Liss, Inc. [source] Controversies in the management of the cutaneous T cell lymphomasDERMATOLOGIC THERAPY, Issue 5 2009John A. Zic ABSTRACT The primary cutaneous T cell lymphomas (CTCL) encompass all malignancies of the T cell where the skin is the primary organ of involvement. The diagnosis of a CTCL variant can be detoured by a number of obstacles including the slow evolution of the disease into a classic clinical and pathologic pattern. A realistic goal of early stage treatment is to reduce the likelihood of progression to a more advanced stage, not to achieve a cure. No studies have adequately compared the different systemic agents in patients with advanced CTCL so the clinician is left to act in the best interest of the patient with what evidence is available. When using the systemic agents, a "start low and go slow" strategy may offer patients several advantages. Dermatologists are uniquely trained to diagnose and to manage all but the most advanced stage patients with CTCL. [source] Vakzinationstherapie kutaner T-Zell-LymphomeJOURNAL DER DEUTSCHEN DERMATOLOGISCHEN GESELLSCHAFT, Issue 12 2002Vaccination therapy for cutaneous T-cell lymphoma primary cutaneous T cell lymphomas (CTCL); vaccination; antigenic targets Zusammenfassung: Primär kutane T-Zell-Lymphome (CTCL) sind definiert als klonale Proliferation hautinfiltrierender T-Lymphozyten. Unabhängig von der Heterogenität dieser Krankheitsgruppe besteht derzeit keine kurative Therapiemöglichkeit, was zur Entwicklung verschiedener Behandlungsstrategien, einschließlich der Vakzination, führte. Dieser Artikel gibt eine Übersicht über den Entwicklungsstand der Vakzinationstherapie für Lymphome mit besonderer Rücksicht auf die CTCL. Da bisher kein universelles Tumorantigen identifiziert wurde, sind verschiedenste antigene Agenzien (komplette Tumorzellen, Idiotypen, Cancer/Testis-Antigene, Proteine aus tumorassoziierten Mutationen und Mimotope) hinsichtlich ihrer Eignung für die Vakzinationstherapie von CTCL untersucht worden. Die antigene Information dieser Präparationen kann dem körpereigenen Immunsystem über verschiedene Wege (Carrier) dargeboten werden, bisher sind dazu mit Tumorzellen fusionierte dendritische Zellen, Idiotyp-Proteine oder -Peptide sowie DNA- und RNA-Präparationen eingesetzt worden. Da die verwendeten Antigene allesamt schwache Immunogene darstellen, sind Adjuvanzien (dendritische Zellen, immunogene Peptide, Oligonukleotide, Zytokine, virale Vektoren) notwendig, um eine suffiziente Antigenpräsentation und Aktivierung des Immunsystems zu erreichen. Erste klinische Daten bestätigen die prinzipielle Wirksamkeit einer Vakzinationstherapie bei CTCL. Die große Anzahl bisher verwendeter Antigene, Carrier, Adjuvanzien und Applikationsschemen macht die Identifizierung eines optimalen Protokolls jedoch nahezu unmöglich. Da auch die Wechselwirkungen zwischen Lymphom und Immunsystem sehr komplex und nicht vollständig verstanden sind, ist bis zur Einführung der Vakzinationstherapie in die klinische Praxis noch großer Forschungsaufwand nötig. Summary: Primary cutaneous T,cell lymphomas (CTCL) are defined as clonal proliferation of skin-infiltrating T lymphocytes. Despite their heterogeneity, CTCL are generally incurable, which lead to the development of various treatment strategies including vaccination. Here, the attempts to vaccinate against lymphoma will be reviewed with special emphasis on CTCL. Since an universal tumour antigen is not available so far, different targets, including whole tumour cells, idiotypes, cancer/testis antigens, proteins derived from tumour-associated mutations, and mimotopes, have been investigated for their applicability in CTCL vaccination. The antigenic information can be delivered in different ways. So far, tumour cells fused to dendritic cells, idiotypic proteins/peptides and DNA/RNA preparations have been applied in lymphoma. Since most targets are weak immunogens, adjuvants and other helpers, including dendritic cells, immunogenic peptides and oligonucleotides, cytokines, and viral vectors, are required to enable proper presentation of the antigens and sufficient activation of the immune system. Although first data from CTCL patients prove the suitability of vaccination in CTCL therapy, the number of available antigens, carriers, adjuvants and application schemes creates a multitude of vaccine formulations and identification of the best-suited approach difficult. Furthermore, the relationship between lymphoma and the host immune system is complex and still not completely understood. In consequence, CTCL vaccination requires a lot of research to be done before its breakthrough. [source] | ||||||||||