Tape-strip transcriptomics identify immune signatures in cutaneous T-cell lymphoma distinct from benign inflammatory...

Primary cutaneous T-cell lymphomas (CTCL), particularly in their early stages, frequently present with clinical and histopathologic features that overlap with atopic dermatitis (AD) and psoriasis, contributing to diagnostic delay and ineffective, or even deleterious, treatment approaches. Minimally invasive molecular tests capable of distinguishing CTCL from benign inflammatory dermatoses are thus urgently needed.

We sought to determine whether tape-strip transcriptomics can detect disease-specific signatures distinguishing early-stage CTCL from AD, psoriasis, and healthy control (HC) skin.

Bulk RNA sequencing was performed on lesional and nonlesional tape strips from skin of patients with mycosis fungoides (MF; n = 18), AD (n = 36), psoriasis (n = 32), and HC (n = 30).

Principal component analysis revealed distinct clustering of MF, AD, and psoriasis lesional skin relative to HC. MF displayed a mixed immune profile, contrasting with the strong T_H2 and T_H17/T_H22 immune polarization of AD and psoriasis, respectively. Upregulated MF genes were involved in immune checkpoint regulation (CTLA4, ICOS), lymphoid trafficking (CCR7, CCR8), antigen presentation (HLA-DRA, LAMP3), T-cell survival (TNFSF13B, BIRC3), metabolism (BCAT1, ENPP4, LIPA), and cell structure and homeostasis (CLIC2, DOCK10, EPB41L3, MCOLN2, MS4A14, S100B). We identified a 5-marker gene classifier (including IL36A) that accurately distinguished MF from both AD and psoriasis, which was validated in an independent dataset.

By capturing MF-specific signatures that are distinct from AD and psoriasis, tape stripping has the potential to serve as a diagnostic tool to help differentiate MF from its nonmalignant mimickers.