Abstract LB133: Fusobacteria nucleatum and Lactobacteria gasseri-johnsonii associated to PD-1 expression in head and neck cancer patients

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Abstract Introduction: The overall response rates of immune-checkpoint inhibitors (ICI) in head and neck squamous cell carcinoma (HNSCC) range from only 13%-18%. The potential immune-related toxicities of ICI and their high cost have urged the search for prospectively validated predictive biomarkers of response to ICI in HNSCC patients. We and others have previously shown that the oral microbiome, including Fusobacterium nucleatum, Lactobacillus gasseri/johnsonii, and Lactobacillus vaginalis in saliva from Human Papilloma Virus (HPV) positive and HPV negative patients, may be crucial for tumor development and progression, treatment-related toxicity, and disease recurrence. Here, we explore the links between the tissue microbiome, PD-1 expression, and HPV status in HNSCC patients. Methods: We used high-resolution microbiome profiling to investigate microbial species present in samples from PD-1 positive and PD-1 negative HNSCC patients. We performed 16S rRNA sequencing in tissue samples from a discovery cohort of 23 HNSCC patients and 8 normal epithelium controls. We subsequently used the Axiom Microbiome Array (ThermoFisher), which harbors a total of 1.38 million probes, to assess microbial composition in a validation cohort of nine (9) PD-1 positive HNSCC, nine (9) PD-1 negative HNSSC, two (2) PD-1 positive normal oral epithelium, and two (2) PD-1 negative normal oral epithelium tissue samples. Results: We found a statistically significant difference in total microbial richness when stratifying cancer and normal tissue by PD-1 expression and HPV status (P< 0.0001), while strata of cancer versus normal tissue displayed no statistical difference in observed microbial richness. We found no difference in species abundance when comparing normal and tumor epithelium. We observed a reduction in overall microbiome composition among PD-1 positive patients when compared to PD-1 negative patients, and an increase in abundance of Bacteroidetes, Firmicutes and Fusobacteriacommunities in PD-1 positive patients, including Fusobacteria nucleatum and Lactobacteria gasseri-johnsonii. Conclusion: Microbiome modulation of PD-1/PD-L1 pathway induction and downstream maintenance of immune tolerance may directly impact the response of HPV positive and HPV negative patients to ICI. The overall biota reduction paired with an increase in specific bacterial communities we found in PD-1 positive patients suggest an important immunomodulatory role, which warrant further study to determine if the tissue microbiome plays a role in ICI treatment response among HNSCC patients. Citation Format: Laura Palmieri, Kelvin Navarro, Anne Jedlicka, Amanda Dziedzic, James White, Mariana Brait, Wayne Koch, Filipa Godoy-Vitorino, David Sidransky, Rafael E. Guerrero-Preston. Fusobacteria nucleatum and Lactobacteria gasseri-johnsonii associated to PD-1 expression in head and neck cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_2):Abstract nr LB133.

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