052 Staphylococcal enterotoxin promotes the development and maintenance of the skin lesions in cutaneous T cell lymphoma

Cutaneous T cell lymphoma (CTCL) has long been known to have a strong association with Staphylococcus aureus (SA) colonization. Eradication of SA is beneficial to CTCL patients. However, how SA colonization contributes to the pathogenesis of CTCL is poorly characterized. Here, we evaluated the SA colonization in the lesional and nonlesional skin of a cohort of 67 CTCL patients. Skin bacterial culture showed SA colonization in 34.3% of patients. The percentage of SA colonization increased along with the progression of the disease stage. The clinicopathological analysis revealed a positive correlation between SA colonization and dermal eosinophil infiltration in CTCL skin lesions. In most CTCL patients, SA simultaneously presented on the lesional and nonlesional skin and produced the same types of enterotoxins. Further skin microbiome analysis by 16S ribosomal DNA sequencing revealed that the abundance of Staphylococcaceae was markedly greater on lesional than on nonlesional skin. An inverse correlation was identified between the abundance of Staphylococcaceae and the microbial diversity. Furthermore, staphylococcal enterotoxin B (SEB) was the most frequently detected enterotoxins in our patients and presented in 17.4% SA isolates. Recombinant SEB triggered remarkable cell growth of peripheral blood mononuclear cells (PBMCs) from both healthy donors and leukemic CTCL patients. However, the transcriptional programs induced by SEB were completely different between PBMCs from healthy donors and leukemic CTCL patients. SEB stimulated an increase in CD4+ memory T cells and IL13 expression in CTCL patients, whereas an increase of CD8+ memory T cells and γδ T cells coupled with an anti-bacterial response was seen in healthy donors upon SEB stimulation. These findings confirmed that SA colonization is common in CTCL patients and suggested that SA contributed to the development and persistence of CTCL skin lesions via enterotoxin. These results provide new insights into the association between SA and CTCL and may pave the way for future anti-SA treatment in CTCL.