title: Malignant inflammation in cutaneous T-cell lymphoma-a hostile takeover.
abstract: Cutaneous T-cell lymphomas (CTCL) are characterized by the presence of chronically inflamed skin lesions containing malignant T cells. Early disease presents as limited skin patches or plaques and exhibits an indolent behavior. For many patients, the disease never progresses beyond this stage, but in approximately one third of patients, the disease becomes progressive, and the skin lesions start to expand and evolve. Eventually, overt tumors develop and the malignant T cells may disseminate to the blood, lymph nodes, bone marrow, and visceral organs, often with a fatal outcome. The transition from early indolent to progressive and advanced disease is accompanied by a significant shift in the nature of the tumor-associated inflammation. This shift does not appear to be an epiphenomenon but rather a critical step in disease progression. Emerging evidence supports that the malignant T cells take control of the inflammatory environment, suppressing cellular immunity and anti-tumor responses while promoting a chronic inflammatory milieu that fuels their own expansion. Here, we review the inflammatory changes associated with disease progression in CTCL and point to their wider relevance in other cancer contexts. We further define the term "malignant inflammation" as a pro-tumorigenic inflammatory environment orchestrated by the tumor cells and discuss some of the mechanisms driving the development of malignant inflammation in CTCL.
authors.affiliation: Department of Immunology and Microbiology, University of Copenhagen, Blegdamsvej 3c, DK-2200, Copenhagen N, Denmark. thorkr@sund.ku.dk.
authors.forename: Thorbjørn
authors.initials: T
authors.lastname: Krejsgaard
authors.affiliation: Department of Dermatology, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Lise M
authors.initials: LM
authors.lastname: Lindahl
authors.affiliation: School of Veterinary Medicine and Science, University of Nottingham, Loughborough, UK.
authors.forename: Nigel P
authors.initials: NP
authors.lastname: Mongan
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Mariusz A
authors.initials: MA
authors.lastname: Wasik
authors.affiliation: Division of Dermatology, University of Ottawa, Ottawa, ON, Canada.
authors.forename: Ivan V
authors.initials: IV
authors.lastname: Litvinov
authors.affiliation: Department of Dermatology, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Lars
authors.initials: L
authors.lastname: Iversen
authors.affiliation: James J. Peters VA Medical Center, Veterans Affairs, Bronx, NY, USA.
authors.forename: Erik
authors.initials: E
authors.lastname: Langhoff
authors.affiliation: Department of Immunology and Microbiology, University of Copenhagen, Blegdamsvej 3c, DK-2200, Copenhagen N, Denmark.
authors.forename: Anders
authors.initials: A
authors.lastname: Woetmann
authors.affiliation: Department of Immunology and Microbiology, University of Copenhagen, Blegdamsvej 3c, DK-2200, Copenhagen N, Denmark. ndum@sund.ku.dk.
authors.forename: Niels
authors.initials: N
authors.lastname: Odum
mesh_terms: D000818:Animals; D002450:Cell Communication / Q000235:genetics / Q000276:immunology; D002465:Cell Movement / Q000276:immunology; D016207:Cytokines / Q000378:metabolism; D018450:Disease Progression; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007111:Immunity, Cellular / Q000187:drug effects / Q000276:immunology; D007113:Immunity, Innate; D007249:Inflammation / Q000150:complications / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D016410:Lymphoma, T-Cell, Cutaneous / Q000188:drug therapy / Q000209:etiology* / Q000378:metabolism* / Q000473:pathology; D015398:Signal Transduction; D017154:Stromal Cells / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism; D059016:Tumor Microenvironment / Q000276:immunology
chemical_list: D016207:Cytokines
keywords: Cancer; Cutaneous T-cell lymphoma; Infection; Inflammation; Malignant T cells; Mycosis fungoides; Pathogenesis; Sézary syndrome