The skin microbiome stratifies patients with cutaneous T cell lymphoma and determines event-free survival.

in NPJ biofilms and microbiomes by Philipp Licht, Nazzareno Dominelli, Johannes Kleemann, Stefan Pastore, Elena-Sophia Müller, Maximilian Haist, Kim Sophie Hartmann, Henner Stege, Matthias Bros, Markus Meissner, Stephan Grabbe, Ralf Heermann, Volker Mailänder

TLDR

  • The study investigates the role of the skin microbiome in the development and progression of mycosis fungoides (MF), a type of skin cancer. The study found that some MF patients had a disrupted skin microbiome, which allowed harmful bacteria to grow and produce harmful substances. This disruption was linked to a reduced ability of the immune system to fight off the bacteria and a higher risk of the cancer spreading. The study suggests that targeting the skin microbiome with treatments could help prevent MF from spreading.

Abstract

Mycosis fungoides (MF) is the most common entity of Cutaneous T cell lymphomas (CTCL) and is characterized by the presence of clonal malignant T cells in the skin. The role of the skin microbiome for MF development and progression are currently poorly understood. Using shotgun metagenomic profiling, real-time qPCR, and T cell receptor sequencing, we compared lesional and nonlesional skin of 20 MF patients with early and advanced MF. Additionally, we isolated Staphylococcus aureus and other bacteria from MF skin for functional profiling and to study the S. aureus virulence factor spa. We identified a subgroup of MF patients with substantial dysbiosis on MF lesions and concomitant outgrowth of S. aureus on plaque-staged lesions, while the other MF patients had a balanced microbiome on lesional skin. Dysbiosis and S. aureus outgrowth were accompanied by ectopic levels of cutaneous antimicrobial peptides (AMPs), including adaptation of the plaque-derived S. aureus strain. Furthermore, the plaque-derived S. aureus strain showed a reduced susceptibility towards antibiotics and an upregulation of the virulence factor spa, which may activate the NF-κB pathway. Remarkably, patients with dysbiosis on MF lesions had a restricted T cell receptor repertoire and significantly lower event-free survival. Our study highlights the potential for microbiome-modulating treatments targeting S. aureus to prevent MF progression.

Overview

  • The study investigates the role of the skin microbiome in the development and progression of mycosis fungoides (MF), the most common entity of cutaneous T cell lymphomas (CTCL).
  • The study compares lesional and nonlesional skin of 20 MF patients with early and advanced MF using shotgun metagenomic profiling, real-time qPCR, and T cell receptor sequencing. Additionally, the study isolates Staphylococcus aureus and other bacteria from MF skin for functional profiling and to study the S. aureus virulence factor spa. The study identifies a subgroup of MF patients with substantial dysbiosis on MF lesions and concomitant outgrowth of S. aureus on plaque-staged lesions, while the other MF patients had a balanced microbiome on lesional skin. Dysbiosis and S. aureus outgrowth were accompanied by ectopic levels of cutaneous antimicrobial peptides (AMPs), including adaptation of the plaque-derived S. aureus strain. Furthermore, the plaque-derived S. aureus strain showed a reduced susceptibility towards antibiotics and an upregulation of the virulence factor spa, which may activate the NF-κB pathway. Remarkably, patients with dysbiosis on MF lesions had a restricted T cell receptor repertoire and significantly lower event-free survival. The study aims to understand the role of the skin microbiome in MF development and progression and to identify potential targets for microbiome-modulating treatments to prevent MF progression.

Comparative Analysis & Findings

  • The study identifies a subgroup of MF patients with substantial dysbiosis on MF lesions and concomitant outgrowth of S. aureus on plaque-staged lesions, while the other MF patients had a balanced microbiome on lesional skin. Dysbiosis and S. aureus outgrowth were accompanied by ectopic levels of cutaneous antimicrobial peptides (AMPs), including adaptation of the plaque-derived S. aureus strain. Furthermore, the plaque-derived S. aureus strain showed a reduced susceptibility towards antibiotics and an upregulation of the virulence factor spa, which may activate the NF-κB pathway. Remarkably, patients with dysbiosis on MF lesions had a restricted T cell receptor repertoire and significantly lower event-free survival. The study highlights the potential for microbiome-modulating treatments targeting S. aureus to prevent MF progression.

Implications and Future Directions

  • The study's findings suggest that dysbiosis and S. aureus outgrowth may play a role in MF development and progression. The study identifies potential targets for microbiome-modulating treatments to prevent MF progression, such as targeting S. aureus virulence factors and modulating the skin microbiome. The study's findings may have implications for the development of new therapies for MF and other CTCLs. Future research should investigate the role of the skin microbiome in MF development and progression in more detail, including the mechanisms underlying dysbiosis and S. aureus outgrowth. Future research should also investigate the efficacy and safety of microbiome-modulating treatments for MF and other CTCLs.
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