AUTHOR=Dey Saptaswa , Vieyra-Garcia Pablo Augusto , Joshi Aaroh Anand , Trajanoski Slave , Wolf Peter 

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

JOURNAL=Frontiers in Immunology

VOLUME=15

YEAR=2024

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2024.1255859

DOI=10.3389/fimmu.2024.1255859

ISSN=1664-3224

ABSTRACT=<p>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. EL4 T-cell lymphoma cells were intradermally grafted on the back of C57BL/6 mice. Animals were treated with conventional therapeutics such as psoralen + UVA (PUVA) or UVB in the presence or absence of topical antibiotic treatment (neomycin, bacitracin, and polymyxin B sulphate) as an adjuvant. Microbial colonisation of the skin was assessed to correlate with disease severity and tumour growth. Triple antibiotic treatment significantly delayed tumour occurrence (<italic>p</italic> = 0.026), which prolonged the survival of the mice (<italic>p </italic>= 0.033). Allocation to phototherapeutic agents PUVA, UVB, or none of these, along with antibiotic intervention, reduced the tumour growth significantly (<italic>p</italic> = 0.0327, <italic>p </italic>≤ 0.0001, <italic>p </italic>≤ 0.0001 respectively). The beta diversity indices calculated using the Bray−Curtis model showed that the microbial population significantly differed after antibiotic treatment (<italic>p </italic>= 0.001). Upon modulating the skin microbiome by antibiotic treatment, we saw an increase in commensal <italic>Clostridium</italic> species, e.g., <italic>Lachnospiraceae</italic> sp. (<italic>p </italic>= 0.0008), <italic>Ruminococcaceae</italic> sp. (<italic>p </italic>= 0.0001)., <italic>Blautia</italic> sp. (<italic>p </italic>= 0.007) and a significant reduction in facultative pathogens <italic>Corynebacterium</italic> sp. (<italic>p </italic>= 0.0009), <italic>Pelomonas</italic> sp. (<italic>p </italic>= 0.0306), <italic>Streptococcus</italic> sp. (<italic>p </italic>≥ 0.0001), <italic>Pseudomonas</italic> sp. (<italic>p </italic>= 0.0358), and <italic>Cutibacterium</italic> sp. (<italic>p </italic>= 0.0237). Intriguingly, we observed a significant decrease in <italic>Staphylococcus aureus</italic> frequency (<italic>p </italic>= 0.0001) but an increase in the overall detection frequency of the <italic>Staphylococcus</italic> genus, indicating that antibiotic treatment helped regain the microbial balance and increased the number of non-pathogenic <italic>Staphylococcus</italic> populations. These study findings show that modulating microbiota by topical antibiotic treatment helps to restore microbial balance by diminishing the numbers of pathogenic microbes, which, in turn, reduces chronic inflammation, delays tumour growth, and increases survival rates in our CTCL model. These findings support the rationale to modulate the microbial milieu during the disease course of CTCL and indicate its therapeutic potential.</p>