A single-cell atlas identifies oncogenic transcriptional programs and immune escape mechanisms in CTCL.

A single-cell RNA-sequencing atlas of over 2 million cells from 116 CTCL patients reveals recurrent oncogenic transcriptional programs and immune escape mechanisms.

• Why it matters: Understanding the transcriptional and microenvironmental features of CTCL can uncover therapeutic vulnerabilities, addressing the limited durable responses in advanced-stage disease.
• What they did: The study compiled the largest CTCL single-cell atlas, identifying GATA3-dependent transcriptional programs linked to disease progression and potential targets such as HDAC, XPO1, CDK9, JAK/CSF1R, and IKZF1/IKZF3.
• The result: Findings highlight transcriptional programs and immune microenvironment components as therapeutic targets, supporting the development of combinatorial strategies including immune checkpoint inhibitors like PD-1.