Lactobacillus kefiranofaciens ZW18 from Kefir enhances the anti-tumor effect of anti-programmed cell death 1 (PD-1) immunotherapy by modulating the gut microbiota

Abstract

Research on probiotics assisting PD-1 inhibitors in anti-tumor therapy has attracted widespread attention. Therefore, it is important to find new probiotic strains with a PD-1 inhibitor promoting effect. This study aims to find a strain with a good promoting effect on PD-1 inhibitor treatment from 5 probiotic strains with the function of modulating the gut microbiota or enhancing immunity. A preclinical study on the effect of probiotics combined with PD-1 inhibitors in murine melanoma was designed. In this study, Lactobacillus kefiranofaciens ZW18 (ZW18) was found to have the best anti-melanoma effect among the probiotic candidates in PD-1 inhibitor treatment. ZW18 inhibited the tumor growth in PD-1-treated mice with an inhibition rate of 66.16% by activating the body's immunity and promoting the tumor CD8⁺ T cell infiltration. Moreover, the supplement of ZW18 optimized the composition of the gut microbiota in mice treated with PD-1 inhibitors, and significantly increased the abundance of Akkermansia, the Prevotellaceae_NK3B31_group and Muribaculum. Collectively, ZW18 could be regarded as a potential candidate strain for promoting tumor immunotherapy. ZW18 combined with PD-1 inhibitors has a possibility of serving as a functional food to assist tumor immunotherapy.