Researchers Identify Immune System โDefect Linked to Rare โSkin Cancer
Bethesda, MD – A new study published November 11, 2025,โค reveals considerably reduced expression of Toll-like receptors 3 (TLR3) and 9 (TLR9) in the skin of individuals with epidermodysplasia verruciformis (EV), a rare geneticโ disorderโข predisposing sufferers to extensive warts and aโค high risk โฃofโ skin cancer. The findings, stemming from a comparative skin analysis, offer potential new avenues forโค understanding and treating this debilitating condition.
EV, affecting an estimatedโฃ 1 in 600,000 individuals globally, arises from mutations in the EVER1/TMC6 and EVER2/TMC8 genes, disrupting cell-mediated immunity. This latest research, conducted by scientists at the National Center for Biotechnology Information (NCBI), demonstrates a criticalโ linkโข between these genetic defects and impaired immune signaling within the skin. โฃSpecifically, the study found diminishedโค TLR3 โฃand TLR9 protein levels in EV-affected skin compared โto healthy controls, suggesting a compromisedโ ability to detect and respond to viral DNA-a key factor in controlling the human papillomavirus โฃ(HPV) infections thatโ drive EV-related skin cancer advancement.
The study involved a detailed analysis of skin samples from individuals diagnosed withโ EV and healthy control subjects. โขResearchers utilized immunohistochemistry to quantify TLR3 and TLR9โฃ expression levels. Results indicated a considerable decrease in both receptors within the epidermis of EV patients.TLR3 recognizes double-strandedโข RNA,โ frequently enough produced during viral replication, while TLR9 detects unmethylated CpG DNA motifs commonly found in viral genomes. โ
“The reduced expression of these TLRs likely contributes to the persistent HPV infection and subsequent malignant transformation observed in EV,” explained โฃa researcher involved inโ the study. “Understanding this immune deficiency is crucial for developing โฃtargeted therapies to boost antiviral immunity and prevent cancer progression.”
Currently, treatment forโ EV focuses on managing symptoms, including wart removal through โขmethods like cryotherapy, laser therapy, or topical medications.However, โthese approaches are often โคineffective โin preventing the development of skin cancers,โฃ especially squamousโ cell carcinoma. The NCBI teamS findingsโค suggest that future therapeutic strategies โขcould focus on restoring TLR3 and TLR9 function, perhaps โthroughโ topical immunomodulators or geneโ therapy, to enhance the body’s โnatural defenses against HPV and reduce cancer risk. Further research is underway to investigate the precise mechanismsโ underlying โTLR downregulation in EV and to explore the feasibility of these novel treatment approaches.