CD5 Expression in CTCL and Its Implications for Anti-CD5 CAR T-Cell Therapy

Area of Science:

• Immunology
• Dermatology
• Oncology

Background:

• Cutaneous T-Cell Lymphomas (CTCL) are skin malignancies with poor outcomes in advanced stages.
• CD5 is a potential target for CAR T-cell therapy in systemic lymphomas, but its role in CTCL is unclear.
• CD7 and CD26 expression is often lost in malignant T cells in CTCL.

Purpose of the Study:

• To analyze CD5 gene expression in mycosis fungoides (MF), the most common CTCL subtype.
• To evaluate CD5 expression in relation to MF clinical presentation (patch/plaque vs. tumor stage).
• To assess the potential of CD5 as a therapeutic target in different MF stages.

Main Methods:

• Single-cell RNA sequencing (scRNA-seq) of 5 patch/plaque MF biopsies, 8 tumor MF biopsies, and 8 healthy control biopsies.
• Analysis of lesion-specific CD5 gene expression on CD4 T cells.
• Subgroup analysis comparing CD5 expression between patch/plaque and tumor stage MF.

Main Results:

• CD5 expression was significantly higher in malignant MF CD4 T cells (21.1%) compared to healthy controls (5.2%).
• Patch/plaque MF biopsies showed higher CD5 expression in CD4 T cells than tumor stage MF biopsies.
• Advanced tumor stage MF exhibited significant CD5 loss (94.3% loss) compared to patch/plaque MF (76.6% loss).

Conclusions:

• CD5 expression in MF is dynamic and dependent on clinical lesion type.
• CD5 may be a viable therapeutic target for early-stage MF (patch/plaque).
• CD5 targeting may be less effective in advanced MF with tumor presentations due to antigen escape.