Project description:Cutaneous T cell lymphoma (CTCL) is characterized by the proliferation of CD4+ T cells in a background of chronic inflammation, where malignant CTCL cells escape immune surveillance and are not eliminated. To study how miRNAs (miRs) regulate T cell exhaustion in this disease, we performed miRseq analysis, qRT-PCR, and in situ hybridization on 45 primary CTCL samples, 3 healthy skin samples, and CTCL cell lines, identifying miR-155-5p, -130b-3p and -21-3p. Moreover, miR-155-5p, -130b-3p, and -21-3p positively correlated with immune checkpoint gene expression in lesional skin samples and were enriched in the IL6/JAK/STAT signaling pathway by gene set enrichment analysis.
Project description:Cobomarsen (MRG‐106), an oligonucleotide inhibitor of miR‐155, has been evaluated in a clinical phase 1/2 trial for CTCL. We used lesional skin samples from 6 CTCL patients to identify the critical pathways affected by miR‐155 inhibition in CTCL.