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Life (Basel, Switzerland) Feb 2024The interleukins IL-4 and IL-13 are increasingly recognized contributors to the pathogenesis of cutaneous T cell lymphomas (CTCLs), and their role in disease-associated... (Review)
Review
The interleukins IL-4 and IL-13 are increasingly recognized contributors to the pathogenesis of cutaneous T cell lymphomas (CTCLs), and their role in disease-associated pruritus is accepted. The prevailing Th2 profile in advanced CTCL underscores the significance of understanding IL-4/IL-13 expression dynamics from the early stages of disease, as a shift from Th1 to Th2 may explain CTCL progression. Targeted agents blocking key cytokines of type 2 immunity are established therapeutics in atopic disorders and have a promising therapeutic potential in CTCL, given their involvement in cutaneous symptoms and their contribution to the pathogenesis of disease. IL-4, IL-13, and IL-31 are implicated in pruritus, offering therapeutic targets with dupilumab, tralokinumab, lebrikizumab, and nemolizumab. This review analyzes current knowledge on the IL-4/IL-13 axis in mycosis fungoides and Sezary syndrome, the most common types of CTCL, examining existing literature on the pathogenetic implications with a focus on investigational treatments. Clinical trials and case reports are required to shed light on novel uses of medications in various diseases, and ongoing research into the role of IL-4/IL-13 axis blockers in CTCL therapy might not only improve the management of disease-related pruritus but also provide in-depth insights on the pathophysiologic mechanisms of CTCL.
PubMed: 38398754
DOI: 10.3390/life14020245 -
Dermatologie (Heidelberg, Germany) Oct 2022Primary cutaneous lymphomas (CL) are highly radiosensitive. Therefore, radiotherapy is an integral part of multimodality treatment. (Review)
Review
BACKGROUND
Primary cutaneous lymphomas (CL) are highly radiosensitive. Therefore, radiotherapy is an integral part of multimodality treatment.
AIM
The present work provides an overview of indications, technical developments, and dose concepts for total skin electron beam therapy (TSEBT), local radiotherapy as well as maintenance therapy, and current combination studies regarding cutaneous T‑ and B‑cell lymphomas.
MATERIALS AND METHODS
We performed a selective literature search in the PubMed database on the topic of radiotherapy for CL and a search for current studies using clinicaltrials.gov. Furthermore, we describe our own treatment strategies and summarize national and international guidelines.
RESULTS
Low-dose TSEBT is nationally and internationally recommended as an alternative to conventional 36 Gy TSEBT. The main advantages are better tolerability, the possibility of retreatment, a shorter treatment course (approximately 3 weeks), and a short time to response. In current studies, TSEBT is usually delivered to a total dose of 12 Gy and combined with immunotherapy and epigenetic therapy. Local radiotherapy is indicated for mycosis fungoides (MF) tumors and is a curative treatment regimen for other CL, particularly primary cutaneous B‑cell lymphomas.
CONCLUSION
TSEBT is a very effective treatment for MF and is a highly effective palliative treatment, leading to rapid symptom relief and improvement in quality of life. It is an important treatment option, especially in patients with extensive generalized lesions or advanced tumor stage. Local radiation is used as part of TSEBT for tumors and as a boost to undertreated areas. Other CLs are primarily curable with local radiotherapy.
Topics: Humans; Lymphoma, B-Cell; Mycosis Fungoides; Quality of Life; Skin; Skin Neoplasms
PubMed: 36018330
DOI: 10.1007/s00105-022-05046-w -
Archivum Immunologiae Et Therapiae... Apr 2015Chemokines are small molecules that induce chemotaxis and activation of certain subsets of leukocytes. The expression patterns of chemokines and chemokine receptors are... (Review)
Review
Chemokines are small molecules that induce chemotaxis and activation of certain subsets of leukocytes. The expression patterns of chemokines and chemokine receptors are specific to certain organs and cells. Therefore, chemokines are important to elucidate the mechanism of organ-specific human diseases. CCL17 expressed by Langerhans cells, blood endothelial cells, and fibroblasts plays a key role in attracting Th2 cells and tumor cells of adult T-cell leukemia/lymphoma and mycosis fungoides/Sézary syndrome into the skin, developing various Th2-type inflammatory skin diseases as well as cutaneous lymphoma. CCL11 and CCL26 expressed by skin-resident cells, such as fibroblasts, blood endothelial cells, and keratinocytes, induce infiltration of CCR3-expressing cells such as Th2 cells and eosinophils. CCL11 may also serve as an autocrine as well as a paracrine in anaplastic large cell lymphoma. CX3CL1 expressed on blood endothelial cells leads to infiltration of CX3CR1(+) immune cells, such as mast cells, neutrophils, and macrophages, playing important roles in wound healing, tumor immunity, and vasculitis. Biologics targeting chemokines and their receptors are promising strategies for various skin diseases that are resistant to the current therapy.
Topics: Animals; Biological Therapy; Cell Communication; Chemokines; Chemotaxis; Eosinophils; Humans; Immunity, Cellular; Molecular Targeted Therapy; Neoplasms; Skin Diseases; T-Lymphocytes; Th1-Th2 Balance; Vasculitis
PubMed: 25182982
DOI: 10.1007/s00005-014-0313-y -
Cytometry. Part B, Clinical Cytometry Mar 2021This review discusses the definition and major categories of cutaneous T-cell lymphoma, Sézary syndrome and mycosis fungoides, and the role of immunophenotyping in... (Review)
Review
This review discusses the definition and major categories of cutaneous T-cell lymphoma, Sézary syndrome and mycosis fungoides, and the role of immunophenotyping in their diagnosis. The following key points are raised: (a) Sézary syndrome and mycosis fungoides cells most often have a characteristic CD3+ CD4+ CD7- and/or CD26- immunophenotype. (b) This immunophenotype is not specific, but can assist in the distinction from non-neoplastic T cells and other subtypes of mature T-cell neoplasm. (c) However, small subsets of normal and reactive T-cells can have an overlapping immunophenotype, and can be distinguished by evaluating for additional changes in antigen expression.
Topics: Antigens, CD; Flow Cytometry; Humans; Immunophenotyping; Mycosis Fungoides; Sezary Syndrome; Skin Neoplasms; T-Lymphocytes
PubMed: 32516521
DOI: 10.1002/cyto.b.21888 -
Cancer Management and Research 2023Cutaneous T-Cell Lymphoma (CTCL) is a heterogenous disease that consists of distinct clinicopathologic entities and presentations requiring a unique and expert approach... (Review)
Review
Cutaneous T-Cell Lymphoma (CTCL) is a heterogenous disease that consists of distinct clinicopathologic entities and presentations requiring a unique and expert approach to management. The most common subtype is mycosis fungoides, in which local disease has an excellent prognosis and is often managed with topical therapy alone. More extensive cutaneous involvement as well as involvement of lymph nodes and the peripheral blood (Sezary syndrome) require systemic therapies. Recent years have brought an expansion of therapeutic options, specifically with immune-based approaches that were developed using the knowledge gained regarding the biology and molecular pathology of CTCL. Previous systemic therapies such as retinoids, histone deacetylase inhibitors, and chemotherapeutic agents come with significant toxicity and only short-term response. Newer agents such as mogamulizumab and brentuximab vedotin use a targeted immune-based approach leading to longer periods of response with less systemic toxicity. While still in its infancy, the use of immune checkpoint inhibitors such as nivolumab and pembrolizumab appears promising, and while their current clinical application is limited, early data suggest possible future areas for research of immune manipulation to treat CTCL. Herein, we review these novel immune-based treatment strategies, their superiority over prior systemic options, and the ongoing need for further research and clinical trial enrollment.
PubMed: 37700809
DOI: 10.2147/CMAR.S330908 -
Cytometry. Part B, Clinical Cytometry Mar 2021Flow cytometry of peripheral blood has become the standard tool for the diagnosis and monitoring of Sézary syndrome. However, there is a sense of frustration among... (Review)
Review
Flow cytometry of peripheral blood has become the standard tool for the diagnosis and monitoring of Sézary syndrome. However, there is a sense of frustration among dermatologists and oncologist regarding the challenges in interpreting vague flow cytometry (FC) reports, which often include an array of numbers and percentages that are difficult to interpret and fail to elucidate quantitatively or qualitatively the presence or absence of an abnormal T cell population. From the clinicians' perspective, a report of the flow cytometric evaluation for Sézary syndrome should include the following items: presence or absence of abnormal T-cells, phenotype of abnormal cells, and quantity of abnormal cells to disease burden and for staging.
Topics: Flow Cytometry; Humans; Immunophenotyping; Mycosis Fungoides; Sezary Syndrome; Skin Neoplasms; T-Lymphocytes
PubMed: 32017375
DOI: 10.1002/cyto.b.21870 -
P & T : a Peer-reviewed Journal For... Oct 2018Ivosidenib (Tibsovo) for acute myeloid leukemia; elagolix (Orilissa) for endometriosis; and mogamulizumab-kpkc (Poteligeo) for mycosis fungoides or Sézary syndrome.
Ivosidenib (Tibsovo) for acute myeloid leukemia; elagolix (Orilissa) for endometriosis; and mogamulizumab-kpkc (Poteligeo) for mycosis fungoides or Sézary syndrome.
PubMed: 30271102
DOI: No ID Found -
Genes May 2024Primary cutaneous lymphomas (PCLs) are a heterogeneous group of lymphoproliferative disorders caused by the accumulation of neoplastic T or B lymphocytes in the skin.... (Review)
Review
Primary cutaneous lymphomas (PCLs) are a heterogeneous group of lymphoproliferative disorders caused by the accumulation of neoplastic T or B lymphocytes in the skin. Sézary syndrome (SS) is an aggressive and rare form of cutaneous T cell lymphoma (CTCL) characterized by an erythroderma and the presence of atypical cerebriform T cells named Sézary cells in skin and blood. Most of the available treatments for SS are not curative, which means there is an urgent need for the development of novel efficient therapies. Recently, targeting cancer metabolism has emerged as a promising strategy for cancer therapy. This is due to the accumulating evidence that metabolic reprogramming highly contributes to tumor progression. Genes play a pivotal role in regulating metabolic processes, and alterations in these genes can disrupt the delicate balance of metabolic pathways, potentially contributing to cancer development. In this review, we discuss the importance of targeting energy metabolism in tumors and the currently available data on the metabolism of Sézary cells, paving the way for potential new therapeutic approaches aiming to improve clinical outcomes for patients suffering from SS.
Topics: Humans; Sezary Syndrome; Skin Neoplasms; Energy Metabolism; Animals
PubMed: 38790264
DOI: 10.3390/genes15050635 -
International Journal of Molecular... Mar 2024Extracorporeal photopheresis (ECP) is an apheresis procedure that is conventionally used as a first-line treatment for cutaneous and leukemic subtypes of T-cell... (Review)
Review
Extracorporeal photopheresis (ECP) is an apheresis procedure that is conventionally used as a first-line treatment for cutaneous and leukemic subtypes of T-cell lymphoma, such as Sezary's syndrome and mycosis fungoides. Over the past three decades, its immunotherapeutic properties have been tested on a variety of autoimmune conditions, including many dermatologic diseases. There is ample evidence of ECP's ability to modify leukocytes and alter cytokine production for certain dermatologic diseases that have been refractory to first-line treatments, such as atopic dermatitis. However, the evidence on the efficacy of ECP for the treatment of these dermatologic diseases is unclear and/or lacks sufficient evidence. The purpose of this paper is to review the literature on the utilization and clinical efficacy of ECP in the treatment of several [autoimmune] dermatologic diseases and discuss its applications, guidelines, recommendations, and future implementation for dermatologic diseases.
Topics: Humans; Photopheresis; Skin Neoplasms; Mycosis Fungoides; Blood Component Removal; Sezary Syndrome
PubMed: 38474257
DOI: 10.3390/ijms25053011 -
Cancers Apr 2021Primary cutaneous T-cell lymphomas (CTCLs) constitute a heterogeneous group of diseases that affect the skin. Mycosis fungoides (MF) and Sézary syndrome (SS) account... (Review)
Review
Primary cutaneous T-cell lymphomas (CTCLs) constitute a heterogeneous group of diseases that affect the skin. Mycosis fungoides (MF) and Sézary syndrome (SS) account for the majority of these lesions and have recently been the focus of extensive translational research. This review describes and discusses the main pathobiological manifestations of MF/SS, the molecular and clinical features currently used for diagnosis and staging, and the different therapies already approved or under development. Furthermore, we highlight and discuss the main findings illuminating key molecular mechanisms that can act as drivers for the development and progression of MF/SS. These seem to make up an orchestrated constellation of genomic and environmental alterations generated around deregulated T-cell receptor (TCR)/phospholipase C, gamma 1, (PLCG1) and Janus kinase/ signal transducer and activator of transcription (JAK/STAT) activities that do indeed provide us with novel opportunities for diagnosis and therapy.
PubMed: 33923722
DOI: 10.3390/cancers13081931