Pathological and Oncological Sciences 1.
Dr. Magyar, Balázs
HOSD6M
Semmelweis University, Department of Urology
+36205919661
sonatrax@gmial.com
Microbiome-Derived Biomarkers Predict Response to Immune Checkpoint Inhibitors in Urologic Malignancies
Magyar Balázs1, Juhász János2, Hermann-Váradi Melinda1, Horváth Orsolya3, Soós Edina3, Korda Sára1, Szűcs Miklós1, Nyirády Péter1, Szarvas Tibor4
1: Department of Urology, Semmelweis University, Budapest
2: Faculty of Information Technology and Bionics, Pázmány Péter Catholic University, Budapest
3: Department of Uro-Oncology and Pharmacology, National Institute of Oncology, Budapest
4: Department of Urology, University of Duisburg-Essen, Essen
Szóbeli
Pathological and Oncological Sciences 1.
English
Pathological and Oncological Sciences
Introduction
Immune checkpoint blockade (ICB) has improved outcomes in urothelial and renal cell carcinoma (UC, RCC), yet response rates remain heterogeneous. It is well established that the gastrointestinal microbiome plays a pivotal role in the maturation and modulation of our immune system. The role of the gut microbiome in modulating immune checkpoint inhibitor (ICI) efficacy has recently become a topic of intensive research.
Aims
To profile the stool microbiome of patients with UC and RCC treated with ICIs using integrated taxonomic and metabolic pathway (MP) analyses to identify relevant microbiome-related pathways and predictive markers.
Method
Pre-treatment fecal samples from 19 UC and 11 RCC patients treated with ICIs were analyzed by shotgun metagenomic sequencing followed by taxonomic and functional profiling. LEfSe analysis identified the best predictive taxa and MPs across endpoints. Associations between microbial taxa, metabolic pathways, and clinical outcomes—including overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and disease control rate (DCR)—were examined using a custom scoring system. Correlations between pre-ICI medications and outcomes were also explored.
Results
Taxon-level LEfSe combined with our scoring system identified Bacteroides stercoris and the genera Blautia and Butyricimonas as the strongest negative predictors. MP-level LEfSe revealed five pathways linked to multiple endpoints, including arginine, sucrose, and dTDP-β-D-fucofuranose metabolism. Integrating key contributing species (Akkermansia muciniphila, Bacteroides stercoris, Ruminococcus lactaris) yielded a composite biomarker strongly correlating with all endpoints. ROC analysis showed AUCs of 0.824 (10-month OS), 0.737 (PFS), 0.856 (DCR), and 0.988 (ORR). Pre-therapy antibiotic use, especially within three months, was associated with worse outcomes.
Conclusion
This study identifies key microbial biomarkers associated with clinical outcomes in UC and RCC patients treated with ICIs. It confirms the role of Akkermansia muciniphila and highlights novel candidates, including Bacteroides stercoris and a three-taxon composite marker with strong predictive value.
Funding
Supported by the Hungarian Ministry of Culture and Innovation and the National Research, Development and Innovation Fund (K139059).
Semmelweis University
Prof. Dr. Szarvas Tibor
I do not give consent to the publication of my abstract on the website of the congress.
in doctoral studies before complex exam (PhD)
Szabad
elfogadva
szóbeli
nem rendelkezett róla
9787
15:15
15:25