Abstract 6532: Higher <i>Lachnoanaerobaculum</i> abundance in the oral microbiome go along with higher levels of tumor-infiltrating lymphocytes and improved survival in head-and-neck cancer patients undergoing radiotherapy

Recent studies suggest a role for the microbiome in modulating anti-cancer treatment responses, but the impact of the oral microbiome on head-and-neck squamous cell carcinoma (HNSCC) treatment outcomes remains largely unexplored, prompting our analysis of its potential influence following definitive (chemo)radiation. Saliva samples of two independent prospective trials including HNSCC patients undergoing definitive (chemo)radiation were analyzed in terms of the oral microbiome composition before treatment initiation using V3-4 16S rRNA sequencing. Significant findings of the saliva microbiome were validated using information on the intratumoral HNSCC microbiome from The Cancer Genome Atlas (TCGA) database. Immunohistochemistry analyses of tumor-infiltrating lymphocytes (TILs) were carried out to reveal potential differences in the tumor microenvironment depending on microbiome findings. A subset of patients received serial [18F]FMISO-PET imaging as part of a prospective study (n=11) and were analyzed regarding a potential link between their oral microbiome and tumoral hypoxia. A total of 92 HNSCC patients treated with definitive (chemo)radiation were analyzed. Median age was 61 years (IQR, 56-66), most patients were male (n=77, 84%), and oropharyngeal cancer was the most common carcinoma (n=53, 58%). Higher salivary levels of Lachnoanaerobaculum spp. was associated with longer locoregional recurrence-free (p=0.0115) and overall survival (p=0.0417), which remained significant in the multivariable regression analysis (p=0.049974 [locoregional recurrence-free survival], p=0.0187 [overall survival]). Validation using intratumoral data from the TCGA cohort demonstrated an association of higher intratumoral Lachnoanaerobaculum levels with improved overall survival (p=0.0380). Neither the overall prevalence (p&amp;gt;0.9999) nor the time until occurrence of acute higher-grade mucositis (p=0.8414) was influenced by Lachnoanaerobaculum abundance. Patients with higher salivary Lachnoanaerobaculum levels had more CD4-positive stromal (p=0.0269) and CD8-positive intraepithelial TILs (p=0.0123). There was an inverse correlation between higher baseline salivary Lachnoanaerobaculum levels and a prognostically favorable early resolution of intratumoral hypoxia during chemoradiation (r = -0.6514, p=0.0229). High Lachnoanaerobaculum levels in the oral microbiome are associated with better locoregional control, overall survival, and factors predicting improved chemoradiation response in HNSCC patients, such as higher CD8-positive TILs levels and early hypoxia resolution. While Lachnoanaerobaculum may serve as a prognostic marker for improved treatment outcomes, further research is required on the mechanistic role of Lachnoanaerobaculum. Citation Format: Alexander Rühle, Maté Krausz, Elsa Beatriz Monroy Ordonez, Jannis Heyer, Andreas R. Thomsen, Henning Schäfer, Peter Bronsert, Rebecca Kesselring, Ali Al-Ahmad, Andreas Knopf, Anca-Ligia Grosu, Michele Proietti, Michael Henke, Christopher Berlin, Nils Henrik Nicolay. Higher Lachnoanaerobaculum abundance in the oral microbiome go along with higher levels of tumor-infiltrating lymphocytes and improved survival in head-and-neck cancer patients undergoing radiotherapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 6532.