Researchers at The University of Texas MD Anderson Cancer Center identified an immune pathway that may promote the progression of oral precancerous lesions into head and neck squamous cell carcinoma, according to a July 16 announcement. The study, published in Cancer Research, was led by Yu Leo Lei, D.D.S., Ph.D., associate professor of Head & Neck Surgery, Cancer Biology and Translational Molecular Pathology; along with co-first authors Wang Gong, Ph.D., research scientist in Cancer Biology, and Hülya Taner, D.D.S., Ph.D., at the University of Michigan School of Dentistry.
The findings highlight potential biomarkers for high-risk precancerous lesions and suggest that targeting a key inflammation signal known as interleukin-1 alpha (IL-1α) could help restore immune surveillance and prevent high-risk lesions from becoming invasive. “Identifying immune shifts in the precancerous stage provides an opportunity to intervene earlier and prevent high-risk lesions from progressing into cancer,” Lei said. “These results suggest that IL-1α may actively create an immunosuppressive environment and that blocking this signal early on could give the immune system an opportunity to regain control, ultimately improving patient outcomes and quality of life.”
Some abnormal precancerous growths in the lining of the mouth can become cancerous despite preventive surgical removal and constant monitoring. Tools to identify which lesions pose the greatest risk are limited. To address this gap, researchers developed preclinical models to explore underlying immune changes that could help identify lesions with a higher risk of progression.
The study found suppressive myeloid cells appear early on with higher levels of IL-1α, SLC2A1 and SPP1 activity but weak interferon signaling. Similar changes were noticed in human lesions that later became cancerous. Cells with SOX2 amplification release CCL2—an inflammatory signal recruiting myeloid cells—pushing them toward an immunosuppressive state marked by high IL-1α levels but low type-I interferon target genes. IL-1α also weakens the STING pathway involved in recognizing abnormal cells.
Blocking the IL-1α receptor reduced immunosuppressive cells, delayed tumor development, and improved survival in preclinical models. This suggests such intervention could be a potential therapeutic strategy for oral cancer prevention.
The current World Health Organization histology grading system does not reliably predict whether oral precancerous lesions will develop into cancer. The study identified novel biomarkers for more effective risk stratification among patients with these lesions. Future studies will evaluate these biomarkers’ specificity and sensitivity in larger patient groups while providing rationale for clinical trials testing interventions inhibiting the IL-1α pathway.
