Ultrasound-Stimulated Microbubble Cavitation Combined With Anti-PD-L1 Blockade Inhibits the Progression of MC38 Tumors and Alters the Composition of Gut Microbiota in Mice

TL;DR

Combining ultrasound-stimulated microbubble cavitation with anti-PD-L1 therapy in mice reduces tumor growth and changes gut microbiota composition.

Contribution

This study reveals how combining USMC with anti-PD-L1 therapy alters gut microbiota and improves tumor treatment outcomes in mice.

Findings

Combining USMC and anti-PD-L1 therapy significantly reduces tumor volume and weight in mice.

The treatment combination prolongs survival and alters gut microbiota composition.

Four bacterial genera are positively linked to treatment efficacy in the combined therapy group.

Abstract

PD-L1 inhibitor immunotherapies have achieved significant advances in cancer treatment, yet only a subset of patients benefits, with response rates varying widely. Previous studies demonstrated that ultrasonic-stimulated microbubble cavitation (USMC) enhances the antitumor effects of PD-L1 inhibitors, suppressing tumor progression and prolonging survival in murine models. Given the gut microbiome's critical role in antitumor immunity and treatment efficacy, the interplay between USMC, immunotherapy, and gut microbiota remains poorly understood. To investigate this relationship, we conducted 16S rDNA sequencing to analyze the gut microbiota in mice across four treatment groups: control (ck), USMC group (um), PD-L1 inhibitor (pdl1), and USMC+PD-L1 inhibitor (um-pdl1). Our results revealed significant variations in gut microbial composition and abundance among the groups. Notably, we identified a correlation between commensal microbiota profiles and therapeutic responses. Mice treated with pdl1 alone or in combination with um exhibited marked reductions in tumor volume and weight, along with prolonged survival and concurrent shifts in gut microbiota. Multimatrix correlation analysis further identified four bacterial genera (Akkermansia, Bacteroides, Escherichia-Shigella, and Enterococcus) positively associated with treatment efficacy in the pdl1 and um-pdl1 groups. In summary, our findings preliminarily reveal substantial alterations in gut microbiota following tumor development, with the um-pdl1 regimen exerting a pronounced influence on microbial composition.

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