Altered skin microbiome along with skin barrier changes in cutaneous T cell lymphoma

Summary: Abstract Body: Cutaneous T-cell lymphomas (CTCLs) represent a heterogeneous group of lymphoid malignancies arising from skin-homing T cells, with mounting evidence linking their pathogenesis to the host microbiome. However, the specific role of cutaneous microbiota dysbiosis in the development of CTCL remains ambiguous, particularly among Asian populations. In this study, we conducted 16S and ITS sequencing of skin swab samples from 72 CTCL patients and 26 matched healthy controls (HCs) to characterize bacterial and fungal communities. We observed alterations in the skin microbiome among CTCL patients when compared to HCs, with these changes being particularly pronounced in advanced CTCL cases (P:0.002). Notably, there was a significant increase in the relative abundances of Staphylococcus aureus (SA, P<0.0001) and Mycosphaerella tassiana in advanced CTCL patients, which correlated with elevated mSWAT and pruritus scores, as well as high levels of lactic dehydrogenase. Conversely, we noted a marked decrease in the relative abundances of Cutibacterium acnes(P:0.02) and Malassezia globosa (0.007) in advanced CTCL patients, which was inversely correlated with the severity of CTCL and the abundance of SA. Furthermore, a random forest model identified the ten most discriminatory species, including the aforementioned four, capable of differentiating advanced CTCL from early CTCL, achieving a mean prediction AUC of 0.752. Additionally, in vitro experiments demonstrated that the expression of skin barrier genes, particularly filaggrin and loricrin (P<0.0001), was downregulated in HaCaT cells following treatment with the supernatant from CTCL cell lines (Myla and Hut 78). Immunostaining of skin biopsies revealed that decreased expression of filaggrin in the epidermis was associated with increased expression of GATA3 and TOX in malignant T cells (All P<0.05). Our findings suggest that the skin microbiome undergoes alterations during CTCL progression, coinciding with an impaired skin barrier, potentially linked to malignant T cells exhibiting a T helper cell-2 phenotype. Huizhong Wang¹, Ruojun Wang¹, Yang Wang¹, Jingru Sun¹ 1. Dermatology and Venerology, Peking University First Hospital, Beijing, Beijing, China. Innate Immunity, Microbiology, and Microbiome