ena-STUDY-YALE-30-11-2020-17:29:05:684-46
MALIGNANT T CELL ACTIVATION BY A BACILLUS SPECIES ISOLATED FROM CUTANEOUS T CELL LYMPHOMA LESIONS
Cutaneous T cell lymphoma (CTCL is a life-debilitating malignancy of lymphocytes homing to the skin. While CTCL is thought to arise from a combination of genetic, epigenetic and environmental factors, specific triggers are unclear.  The skin is colonized by a unique microbiota and is heavily influenced by its interactions. We hypothesized that adaptive immune responses to skin commensals leads to clonal T cell proliferation and transformation in the appropriate genetic background. We therefore collected lesional and non-lesional skin microbiota from CTCL patients to study T cell interactions using skin T cell explants and peripheral, skin-homing CD4+ T cells.  By various methods, we identified Bacillus safensis in CTCL lesions, a rare human commensal in healthy skin, and demonstrated it can induce malignant T cell activation and cytokine secretion. Taken together, our data suggest microbial triggers in the skin microbiota of CTCL patients as potential instigators of tumorigenesis.
Cutaneous T cell lymphoma (CTCL is a life-debilitating malignancy of lymphocytes homing to the skin. While CTCL is thought to arise from a combination of genetic, epigenetic and environmental factors, specific triggers are unclear.  The skin is colonized by a unique microbiota and is heavily influenced by its interactions. We hypothesized that adaptive immune responses to skin commensals leads to clonal T cell proliferation and transformation in the appropriate genetic background. We therefore collected lesional and non-lesional skin microbiota from CTCL patients to study T cell interactions using skin T cell explants and peripheral, skin-homing CD4+ T cells.  By various methods, we identified Bacillus safensis in CTCL lesions, a rare human commensal in healthy skin, and demonstrated it can induce malignant T cell activation and cytokine secretion. Taken together, our data suggest microbial triggers in the skin microbiota of CTCL patients as potential instigators of tumorigenesis.