| Purpose:We sought to investigate the effect of the gut microbiome composition and exosomal programmed death-ligand 1(PD-L1)expression in patients with advanced hepatocellular carcinoma(HCC)receiving PD-1 blockade therapy.Methods:Our study enrolled twelve patients with advanced HCC receiving PD-1 blockade therapy.From March 2017 to March 2019,the fecal and blood samples were collected,and patients were followed up for PFS and OS.The survival curve for the progression free survival(PFS)was performed by the Kaplan-Meier method(log-rank test).Gut microbiome diversity was analyzed using 16 S rRNA sequences.Exosomes were isolated from peripheral blood through ultracentrifugation,and the expression of exosomal PD-L1 was detected by western blot.Results:There were seven responders(three with partial response and four with stable disease)and five non-responders(progressive disease)according to the Evaluation Criteria in Solid Tumors version 1.1(RECIST 1.1)best response criteria.The 16 S rRNA analysis showed that the gut microbiome composition of responders and non-responders were significantly different.Clostridium was more enriched in the response group,whereas Blautia_obeum was more abundant in the non-response group.The progression-free survival(PFS)was significantly prolonged in patients with a high abundance of Clostridium compared to that in the low-abundance group(P=0.047).The expression of PD-L1 in exosomes did not differ among patients showing partial response(PR),stable disease(SD),and disease progression(PD).Conclusion:The gut microbiome composition of responders and non-responders were significantly different.In particular,the abundance of Clostridium and Bloautia_obeum may be related to efficacy and prognosis in advanced hepatocellular carcinoma patients receiving PD-1 blockade therapy.However,plasma exosomal PD-L1 expression may not be related to the efficacy of PD-1 blockade therapy. |
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