Transcriptional Heterogeneity and the Microbiome of Cutaneous T-Cell Lymphoma

Abstract

Cutaneous T-Cell Lymphomas (CTCL) presents with substantial clinical variability and transcriptional heterogeneity. In the recent years, several studies paved the way to elucidate aetiology and pathogenesis of CTCL using sequencing methods. Several T-cell subtypes were suggested as the source of disease thereby explaining clinical and transcriptional heterogeneity of CTCL entities. Several differentially expressed pathways could explain disease progression. However, exogenous triggers in the skin microenvironment also seem to affect CTCL status. Especially Staphylococcus aureus was shown to contribute to disease progression. Only little is known about the complex microbiome patterns involved in CTCL and how microbial shifts might impact this malignancy. Nevertheless, first hints indicate that the microbiome might at least in part explain transcriptional heterogeneity and that microbial approaches could serve in diagnosis and prognosis. Shaping the microbiome could be a treatment option to maintain stable disease. Here, we review current knowledge of transcriptional heterogeneity of and microbial influences on CTCL. We discuss potential benefits of microbial applications and microbial directed therapies to aid patients with CTCL burden.

TOX Expression in Mycosis Fungoides and Sezary Syndrome

“…Airborne toxins and potential carcinogenetic substances have been investigated as possible trigger of the disease with no clear correlation [ 10 ]. Infective agent susceptibility such as Staphylococcus aureus is thought to be involved in MF/SS pathogenesis and progression [ 11 ]. Genetic aberration along with cytokinc and inflammatory cell changes have been proposed as a putative candidate [ 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 ] sometimes providing contradictory results due to the small sample size or the use of different technique of investigation (immunohistochemistry and/or molecular biology analysis).…”

Interleukin-17 Genes Polymorphisms are Significantly Associated with Cutaneous T-cell Lymphoma Susceptibility

“…Interestingly, recent studies of the mouse model have shown that T-cell receptor engagement is an important factor of malignant transformation in CTCL ( 20 ). Moreover, progression of the disease also appeared to be dependent on microbiota ( 20 , 21 ). In addition, Staphylococcus aureus is known as the most common aetiological factor in infections in patients with CTCL, who are colonized by this bacteria in 44% up to 76% ( 22 ).…”

“…In addition, Staphylococcus aureus is known as the most common aetiological factor in infections in patients with CTCL, who are colonized by this bacteria in 44% up to 76% ( 22 ). S. aureus superantigens may exacerbate and/or perpetuate the clonal expansion of the lymphoma concomitantly with spreading cutaneous inflammation ( 21 , 23 ). In addition, staphylococcal enterotoxin A isolates have been shown to induce signal transducer and activator 3 (STAT3) activation and expression of IL-17, which pathway has been hypothesized as one of the oncogenic factors in CTCL ( 3 , 24 ).…”

“…The constant responses of both malignant and benign lymphocytes to the S. aureus inflammation may contribute to carcinogenesis, which would explain why transient, aggressive antibiotic therapy may slow the tumour progression in some cases ( 22 , 27 ). S. aureus eradication may be a novel treatment for advanced MF/SS in the future ( 21 , 28 ).…”

The Role of The Tumor Microbiome in Tumor Development and Its Treatment

“…in CTCL skin and high relative abundance of C. tuberculostearicum in stage IVA1 patients (100). Staphylococcus aureus was shown to contribute to CTCL progression (101).…”