Early inflammation signal drives oral cancer development, highlights path for immunoprevention

UT MD Anderson Research News July 16, 2026

• Researchers identified immune changes in a subset of oral precancerous lesions that may be at higher risk for cancer progression
• Cells with high SOX2 expression release a signal that recruits immunosuppressive cells before invasive cancer develops
• Blocking the signal delayed cancer development in preclinical models, suggesting its potential for cancer prevention

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. These results provide insights into how precancers gradually establish an immune tolerance to allow for cancer development.

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.”

Why are oral precancers difficult to manage?

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. Therefore, the researchers developed preclinical models to explore the underlying immune changes that could help identify lesions with a higher risk of progression.

What early immune changes happen in lesions before they become invasive?

The researchers identified suppressive myeloid cells that appear early on and have higher levels of IL-1α, SLC2A1 and SPP1 activity but have weak interferon signaling, which normally supports immune defense. They also noticed these similar changes in human lesions that later became cancerous.

Specifically, they found that cells with SOX2 amplification release CCL2, an inflammatory signal that recruits myeloid cells and pushes them toward an immunosuppressive state. This state is marked by high levels of IL-1α, SLC2A1 and SPP1, but low levels of type-I interferon target genes. IL-1α also weakens the STING pathway, which normally helps the immune system recognize abnormal cells.

Blocking the IL-1α receptor reduced the amount of immunosuppressive cells, delayed tumor development and improved survival in preclinical models, suggesting that this approach could be a potential therapeutic strategy for oral cancer prevention.

What does this mean for patients with oral precancerous lesions?

The current WHO histology grading system does not reliably predict whether oral precancerous lesions will develop into cancer. This study identified a set of novel biomarkers that can aid in more effective risk stratification for patients with these lesions.

Future studies will evaluate this particular set of biomarkers in larger patient groups and validate its specificity and sensitivity. This study also provides a rationale for future testing of interventions that inhibit the IL-1α pathway as a preventive treatment in clinical trials. Similarly, a Phase 1 trial led by Moran Amit, M.D., Ph.D., assistant professor of Head & Neck Surgery, showed promising results through immunoprevention for precancerous oral lesions.

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This study was supported in part by the National Institutes of Health and the National Cancer Institute. Lei is a co-founder of Saros Therapeutics and serves on its scientific advisory board. For a full list of collaborating authors, disclosures and funding sources, see the full paper in Cancer Research.