Dynamic microbiome and metabolome analyses reveal the interaction between gut microbiota and anti-PD-1 based immunotherapy in hepatocellular carcinoma
Menée à partir d'échantillons fécaux et d'échantillons sériques prélevés sur 35 patients atteints d'un carcinome hépatocellulaire, cette étude met en évidence une interaction entre le microbiote intestinal et la réponse aux anti-PD-1
Hepatocellular carcinoma (HCC) is a severe disease with high mortality and global incidence. However, the interaction between the gut microbiome and combined immunotherapy for HCC is yet unclear. In this prospective clinical study, patients with unresectable HCC who had not received systemic treatment previously were recruited. Fecal and serum samples were collected at the baseline point and before each subsequent administration as specified. Between October 20, 2019 and February 2, 2021, 61 patients were screened for eligibility, of whom 35 patients were finally included in this study. Alpha diversity of fecal samples from patients who responded to immunotherapy was higher than that of non-responders at baseline. However, the prominent alpha-diversity between responders and non-responders became similar as early as week 6 after treatment. The beta diversity of inter-group did not show significant difference at the 9th week after treatment. Alpha-D-Glucose was the only serum metabolite that differed between the responders and non-responders after 3 months. Responder-enriched Ruminococcus showed a positive correlation with serum galactaric acid, while Klebsiella was positively associated with 3-methylindole and lenticin (all P<0.01). The machine learning classifier based on serum metabolites were more able to discriminate HCC patients who potentially benefited from immunotherapy at baseline (AUC 0.793, 95% CI: 0.632–0.954) than the classifier of gut microbiome. In conclusion, gut microbiome biomarkers are associated with the response to anti-PD-1 based immunotherapy in HCC patients. Classifiers based on gut microbiota and serum metabolites are feasible.
International Journal of Cancer , résumé, 2022