1043 Modulation of the skin microbiome in cutaneous T-cell lymphoma delays tumor growth and increases survival in a murine model

Cutaneous T-cell lymphomas (CTCL) are group of lymphoproliferative disorders of skin-homing T-cells causing chronic inflammation, with impairment of the immune environment leading to severe infections and/or sepsis due to dysbiosis. In this project, we elucidated the host-microbial interaction in CTCL during phototherapeutic treatment regime and if modulation of the skin microbiota could beneficially affect the course of CTCL. EL4 T-cell lymphoma cells were intradermally grafted in the back of C57BL/6 mice. Animals were treated with conventional therapeutics such as psoralen + UVA (PUVA) or UVB in combination or without topical antibiotic treatment (neomycin, bacitracin, and polymyxin B sulfate). Microbial colonization of the skin was assessed to correlate with disease severity and tumor growth. Triple antibiotic treatment significantly delayed tumor occurrence (p=0.026) and growth (p=0.020), which prolonged the survival of mice (p=0.033) irrespective of allocation to therapeutic agents (PUVA, UVB or none). Beta diversity index by the Bray−Curtis model showed that microbial population significantly differed upon antibiotic treatment (p=0.001). Upon modulating the skin microbiome by antibiotic treatment, we saw an increase in commensal Cutibacterium spp. (p=0.041) and a significant reduction in pathogenic Corynebacterium spp. (p=0.0009). Interestingly, we observed an increase in overall Staphylococcus genera but a significant decrease in Staphylococcus aureus frequency (p=0.002), indicating that antibiotic treatment helps regain the microbial balance and increases non-pathogenic Staphylococcus populations. In summary, modulating microbiota by topical antibiotic treatment helps restore microbial balance by diminishing pathogenic microbes, which reduces chronic inflammation, delays tumor growth, and increases survival in our CTCL model. This research supports the rationale for specific antibiotic interventions to modulate the microbial milieu during the disease course of CTCL and indicates therapeutic potential.