Modulation of the skin microbiome in cutaneous T-cell lymphoma delays tumour growth and increases survival in the murine EL4 model.

Cutaneous T-cell lymphomas (CTCL) are a group of lymphoproliferative disorders of skin-homing T cells causing chronic inflammation. These disorders cause impairment of the immune environment, which leads to severe infections and/or sepsis due to dysbiosis. In this study, we elucidated the host-microbial interaction in CTCL that occurs during the phototherapeutic treatment regime and determined whether modulation of the skin microbiota could beneficially affect the course of CTCL.

Blocking STAT3/5 through direct or upstream kinase targeting in leukemic cutaneous T-cell lymphoma.

Leukemic cutaneous T-cell lymphomas (L-CTCL) are lymphoproliferative disorders of skin-homing mature T-cells causing severe symptoms and high mortality through chronic inflammation, tissue destruction, and serious infections. Despite numerous genomic sequencing efforts, recurrent driver mutations have not been identified, but chromosomal losses and gains are frequent and dominant. We integrated genomic landscape analyses with innovative pharmacologic interference studies to identify key vulnerable nodes in L-CTCL.

The molecular and phenotypic makeup of fetal human skin T lymphocytes.

The adult human skin contains a vast number of T cells that are essential for skin homeostasis and pathogen defense. T cells are first observed in the skin at the early stages of gestation; however, our understanding of their contribution to early immunity has been limited by their low abundance and lack of comprehensive methodologies for their assessment. Here, we describe a new workflow for isolating and expanding significant amounts of T cells from fetal human skin.

αβγδ T cells play a vital role in fetal human skin development and immunity.

T cells in human skin play an important role in the immune defense against pathogens and tumors. T cells are present already in fetal skin, where little is known about their cellular phenotype and biological function. Using single-cell analyses, we identified a naive T cell population expressing αβ and γδ T cell receptors (TCRs) that was enriched in fetal skin and intestine but not detected in other fetal organs and peripheral blood.

A deep dive into UV-based phototherapy: Mechanisms of action and emerging molecular targets in inflammation and cancer.

UV-based phototherapy (including psoralen plus UVA (PUVA), UVB and UVA1) has a long, successful history in the management of numerous cutaneous disorders. Photoresponsive diseases are etiologically diverse, but most involve disturbances in local (and occasionally systemic) inflammatory cells and/or abnormalities in keratinocytes that trigger inflammation. UV-based phototherapy works by regulating the inflammatory component and inducing apoptosis of pathogenic cells.

Quality of Life, Anxiety, and Depression in Patients With Early-Stage Mycosis Fungoides and the Effect of Oral Psoralen Plus UV-A (PUVA) Photochemotherapy on it.

Little is known about psychological discomfort and quality of life (QoL) in early stage mycosis fungoides (MF) and the effect of psoralen plus UV-A (PUVA) on it. To evaluate QoL, anxiety, and depression with validated instruments in early stage MF patients and whether PUVA treatment improves it. Patients with stage IA to IIA MF were treated with PUVA twice weekly for 12-24 weeks, followed by maintenance treatment or not, in a prospective randomized clinical trial.

Extracorporeal Photopheresis: A Case of Immunotherapy Ahead of Its Time.

Extracorporeal photopheresis (ECP) is a cell-based immunotherapy that involves the reinfusion of autologous leukocytes after exposure to psoralen and UVA. The treatment has been used for over 30 years, at first on patients with cutaneous T-cell lymphoma (CTCL) and later for the management of patients with graft-versus-host disease (GvHD), sclerosing disorders, atopic dermatitis, and other diseases that may share the common driving factor of a pathogenic T-cell clone or clones in blood circulation. Patients with clinical improvement mount an antigen-specific immune response that may have tolerance traits in the case of GvHD or anticlonal cytotoxic characteristics in the case of CTCL.

From Early Immunomodulatory Triggers to Immunosuppressive Outcome: Therapeutic Implications of the Complex Interplay Between the Wavebands of Sunlight and the Skin.

Phototherapy is an efficient treatment for many cutaneous diseases that involve the activation of inflammatory pathways or the overgrowth of cells with aberrant phenotype. In this review, we discuss recent advances in photoimmunology, focusing on the effects of UV-based therapies currently used in dermatology. We describe the molecular responses to the main forms of photo(chemo)therapy such as UVB, UVA-1, and PUVA that include the triggering of apoptotic or immunosuppressive pathways and help to clear diseased skin.

Cbl-b deficiency provides protection against UVB-induced skin damage by modulating inflammatory gene signature.

Exposure of skin to ultraviolet (UV) radiation induces DNA damage, inflammation, and immune suppression that ultimately lead to skin cancer. However, some of the pathways that regulate these events are poorly understood. We exposed mice to UVB to study its early effects in the absence of Cbl-b, a known suppressor of antitumor immune response in the skin.

STAT3/5-Dependent IL9 Overexpression Contributes to Neoplastic Cell Survival in Mycosis Fungoides.

Purpose: Sustained inflammation is a key feature of mycosis fungoides (MF), the most common form of cutaneous T-cell lymphoma (CTCL). Resident IL9-producing T cells have been found in skin infections and certain inflammatory skin diseases, but their role in MF is currently unknown.

Experimental Design: We analyzed lesional skin from patients with MF for the expression of IL9 and its regulators.