Reprogramming of PD-1+ M2-like tumor-associated macrophages with anti-PD-L1 and lenalidomide in cutaneous T cell lymphoma.

Cutaneous T cell lymphoma (CTCL) is a disfiguring and incurable disease characterized by skin-homing malignant T cells surrounded by immune cells that promote CTCL growth through an immunosuppressive tumor microenvironment (TME). Preliminary data from our phase I clinical trial of anti-programmed cell death ligand 1 (anti-PD-L1) combined with lenalidomide in patients with relapsed/refractory CTCL demonstrated promising clinical efficacy. In the current study, we analyzed the CTCL TME, which revealed a predominant PD-1+ M2-like tumor-associated macrophage (TAM) subtype with upregulated NF-κB and JAK/STAT signaling pathways and an aberrant cytokine and chemokine profile.

Identification of a Distinct miRNA Regulatory Network in the Tumor Microenvironment of Transformed Mycosis Fungoides.

Large cell transformation of mycosis fungoides (LCT-MF) occurs in 20-50% of advanced MF and is generally associated with poor response and dismal prognosis. Although different mechanisms have been proposed to explain the pathogenesis, little is known about the role of microRNAs (miRs) in transcriptional regulation of LCT-MF. Here, we investigated the miR and mRNA expression profile in lesional skin samples of patients with LCT-MF and non-LCT MF using RNA-seq analysis.

MicroRNA Regulation of T-Cell Exhaustion in Cutaneous T Cell Lymphoma.

Cutaneous T cell lymphoma (CTCL) is characterized by a background of chronic inflammation, where malignant CTCL cells escape immune surveillance. To study how microRNAs (miRs) regulate T-cell exhaustion, we performed miR sequencing analysis, qRT-PCR, and in situ hybridization on 45 primary CTCL samples, three healthy skin samples, and CTCL cell lines, identifying miR-155-5p, miR-130b-3p, and miR-21-3p. Moreover, miR-155-5p, miR-130b-3p, and miR-21-3p positively correlated with immune checkpoint gene expression in lesional skin samples and were enriched in the IL-6/Jak/signal transducer and activator of transcription signaling pathway by gene set enrichment analysis.