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Analysis of TME-microbe spatial relationship and gene expression to predict recurrence in oral squamous cell carcinoma

Award Number: R56DE036400
ORGANIZATION: NATIONAL INSTITUTE OF DENTAL AND CRANIOFACIAL RESEARCH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 08/24/2026
PERIOD OF PERFORMANCE END DATE: 08/23/2027

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Analysis of TME-microbe spatial relationship and gene expression to predict recurrence in oral squamous cell carcinoma - ABSTRACT Oral squamous cell carcinoma remains a lethal malignancy with high recurrence rates and limited survival despite AJCC staging–based standard therapy. More than 65% of patients with HNC will develop recurrent or metastatic disease. Current prognostic systems fail to incorporate biologic drivers such as the tumor microenvironment and the microbiome, which likely contribute to recurrence. Preliminary data demonstrate that recurrent oral squamous cell carcinoma tumors harbor a distinct microbiome and intra-tumoral bacterial populations preferentially localize to immunosuppressed regions of the tumor microenvironment, suggesting that bacteria modulate immune architecture and influence recurrence risk. This proposal aims to define the role of the microbiome in shaping the tumor microenvironment and to leverage these interactions to develop a predictive risk stratification tool. Aim 1 will characterize the spatial and functional architecture of recurrent oral squamous cell carcinoma by integrating immune cell distribution with bacterial localization, transcriptomics, and bacterial meta-transcriptomics. Aim 2 will use multi-omics data (transcriptomics, proteomics, bacterial genomics) combined with machine learning to derive a targeted biomarker panel predictive of recurrence-free survival. Aim 3 will validate this panel in a prospective, multi-institutional oral squamous cell carcinoma cohort, testing performance in both surgical and pretreatment biopsy specimens. This study is significant because it addresses the critical unmet need for accurate prognostic tools in oral squamous cell carcinoma by moving beyond histopathologic and demographic features. It is innovative in its integration of spatial multi-omics and microbiome profiling to develop a clinically applicable risk stratification tool. The proposed research will generate the first comprehensive framework of tumor microenvironment-microbe interactions in oral squamous cell carcinoma, advance understanding of microbial contributions to tumor immunosuppression, and establish a predictive tool to improve risk assessment. Successful completion will directly impact clinical management by identifying high- risk patients for treatment intensification and lay the foundation for novel microbiome- and tumor microenvironment-targeted therapeutic strategies in oral squamous cell carcinoma.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = $656,545 )
2026	2026	THE REGENTS OF THE UNIVERSITY OF COLORADO	13001 E 17TH PL STE F428	AURORA	CO	80045	ADAMS	USA	Oral Diseases and Disorders Research	000	1	8/25/2026	NEW	$656,545
														Subtotal = $656,545

Grand Total All Awards = $656,545

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Analysis of TME-microbe spatial relationship and gene expression to predict recurrence in oral squamous cell carcinoma

Award Number: R56DE036400

ORGANIZATION: NATIONAL INSTITUTE OF DENTAL AND CRANIOFACIAL RESEARCH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 08/24/2026

PERIOD OF PERFORMANCE END DATE: 08/23/2027

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