Immune Biomarkers Support Early Risk Stratification in Oral Precancer

Even with surgery and surveillance, clinicians lack reliable tools to identify the highest-risk lesions, and histologic grading is inconsistent in predicting progression. Understanding early immune changes could refine risk stratification and guide prevention. New findings demonstrate an inflammation-driven pathway that may promote malignant transformation and define biomarkers for early risk assessment.

Researchers at The University of Texas MD Anderson Cancer Center identified an immune pathway that may drive the transition of oral precancerous lesions to invasive cancer and outlined a set of candidate biomarkers for risk stratification. The work centers on interleukin-1 alpha (IL-1α) signaling and a myeloid cell phenotype observed at the precancer stage. The study, published on July 14, 2026 in Cancer Research, indicates that these signals could help laboratories distinguish higher-risk lesions earlier in disease evolution.

Mechanistically, investigators observed suppressive myeloid cells emerging early, with elevated IL-1α, SLC2A1, and SPP1 activity alongside weak type I interferon signaling. They further found that SOX2-amplified cells release the chemokine CCL2, recruiting myeloid cells and steering them toward an immunosuppressive state. IL-1α also dampened the STING pathway, a sensor that normally supports immune recognition of abnormal cells, suggesting a coordinated immune-evasion program during malignant transformation.

The team developed preclinical models to probe these immune shifts and documented similar patterns in human lesions that later progressed to cancer. Pharmacologic blockade of the IL-1α receptor reduced immunosuppressive cell populations, delayed tumor development and improved survival in preclinical models. The research was conducted at MD Anderson with contributions from the University of Michigan School of Dentistry.

According to the investigators, the current World Health Organization histology grading system does not reliably predict progression of oral precancerous lesions. The study identifies a biomarker set that may support more effective risk stratification and provides a rationale to test IL-1α–pathway inhibition as a preventive strategy in clinical trials. A separate Phase I study has shown promising results using immunoprevention for precancerous oral lesions.

“Identifying immune shifts in the precancerous stage provides an opportunity to intervene earlier and prevent high-risk lesions from progressing into cancer. 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,” said Yu Leo Lei, D.D.S., Ph.D., associate professor of Head & Neck Surgery, Cancer Biology and Translational Molecular Pathology at The University of Texas MD Anderson Cancer Center.

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The University of Texas MD Anderson Cancer Center