PP201 - GUT MICROBIAL SIGNATURES ASSOCIATED WITH BUTYRATE AND ACETATE PRODUCTION INCREASE IN RESPONDERS AND PREDICT OUTCOMES FOLLOWING ATEZOLIZUMAB PLUS BEVACIZUMAB IN ADVANCED HCC
PP201
GUT MICROBIAL SIGNATURES ASSOCIATED WITH BUTYRATE AND ACETATE PRODUCTION INCREASE IN RESPONDERS AND PREDICT OUTCOMES FOLLOWING ATEZOLIZUMAB PLUS BEVACIZUMAB IN ADVANCED HCC
Y. Jeong1,*, J. Ko1, J. Y. Jhun2, M.-L. Cho2, J. H. Hwang2, S. K. Lee3
1Department of Food and Nutrition, Kyung Hee University, 2Department of Pathology, 3 Department of Internal Medicine, The Catholic University of Korea, Seoul, Korea, Republic Of
Rationale: We conducted a prospective study to identify gut microbial signatures and metabolites associated with treatment response and to evaluate their potential as predictive biomarkers of clinical outcomes following atezolizumab plus bevacizumab (Ate/Bev) therapy in advanced hepatocellular carcinoma (HCC).
Methods: We enrolled 71 patients with advanced HCC treated with first-line Ate/Bev between July 2022 and December 2024 at two tertiary centers. Fecal samples were collected at baseline and at first radiologic assessment and gut microbiome composition was analyzed. Age-matched healthy controls (HC; n=10) were included. An independent cohort of long-term responders (LRes; n=12), defined as sustained response for >12 cycles, was used for validation. In vitro PBMC experiments assessed immunomodulatory effects of SCFA-related metabolites.
Results: At baseline, patients with advanced HCC showed reduced gut microbial diversity compared with HC, with minimal differences between responders (Res) and non-responders (NRes). After treatment, the Res group exhibited increased diversity and compositional shifts, with enrichment of taxa with predicted SCFA–producing capacity. This pattern was maintained and strengthened in LRes, with enrichment of genera linked to acetate and butyrate production. In vitro experiments showed that acetate or butyrate reduced exhaustion-associated CD8⁺ T cells, supporting a potential immunomodulatory role of SCFA-related microbial functions. A consensus set of 22 taxa stratified overall survival.
Conclusion: These findings suggest that SCFA-related gut microbial signatures may associate with treatment response and potentially contribute to enhanced antitumor immunity, highlighting the gut microbiome as a nutrition-modifiable therapeutic target and predictive biomarker in advanced HCC.
Disclosure of Interest: None declared