Skin Barrier and Microbiome of CTCL Patients

Cutaneous T-cell lymphomas (CTCL) are primary T-cell derived cutaneous lymphomas; they represent a group of lymphoproliferative disorders characterized by localization of neoplastic T lymphocytes to the skin. This may result in skin patches and plaques, erythroderma, itch, dry skin and hair loss. In advanced stages tumours in the skin occur often associated with cutaneous and systemic infections. Mycosis fungoides (MF), which is generally indolent in behaviour, and Sézary syndrome (SS), an aggressive and leukemic variant, comprise approximately 53% of all primary cutaneous lymphomas and two-third of CTCL (Willemze et al., 2019). Staphylococcus aureus (S. aureus) and its toxins have been shown to positively correlate with progression and colonize 31% to 76% of patients across all stages and subtypes (Fujii, 2021). Staging and diagnosing the progression of CTCL are key to defining an effective treatment strategy. Current treatment strategies for CTCL are diverse, focusing on anti-tumour activity and infection and/or rash treatment.

CTCL is a group of malignancies that is a subset of non-Hodgkin lymphomas derived from skin-homing T cells with no evidence of extracutaneous disease at the time of diagnosis. MF and SS are the most common CTCL variants (Bastidas Torres et al., 2018; Willemze et al., 2019). MF is the most prevalent (up to 60%) clinical form of CTCL and is characterized by proliferation of malignant skin-homing T cells in a chronic inflammatory environment in the skin. SS is a rare - approx. 2% - leukemic type of CTCL, traditionally defined by the triad of pruritic erythroderma, generalized lymphadenopathy, and clonally related neoplastic T cells with cerebriform nuclei (Sézary cells) in the skin, lymph nodes, and peripheral blood (Girardi et al., 2004; Willemze et al., 2019). CTCL shows, besides MF and SS, several other subtypes and presents in several stages of severity.

The skin barrier of CTCL was observed to be perturbed and hypothetically this influences the microbiome - host interaction.

Only limited information is available about the relationship between CTCL variants, its staging, clinical symptoms and S. aureus colonization. In addition, studies assessed mostly S. aureus presence solely, and not the whole microbiome. This study is set up to investigate the microbiological properties of CTCL patients. Furthermore, the microbiome-host interaction will be studied by investigating skin barrier properties and patient-reported aspects in these patients.

This will provide the rationale and potential impact for a subsequent trial assessing the safety and efficacy of a novel topical compound. It will help determine the population eligible for such study, as well as enriching the population with those most likely to benefit from this therapy.