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. 2025 Dec;17(1):2557978.
doi: 10.1080/19490976.2025.2557978. Epub 2025 Sep 12.

Live biotherapeutic enterococcus lactis MNC-168 promotes the efficacy of immune checkpoint blockade in cancer therapy by activating STING pathway via bacterial membrane vesicles

Yibo Xian  1 , Zhipeng Chen  1 , Zhou Lan  1 , Chenchen Zhang  1 , Hao Sun  2 , Zhenzhen Liu  1 , Ping Kong  1 , Yajun Liang  1 , Yingying Zhao  1 , Si-Yang Maggie Liu  2 , Yiqi Zhou  1 , Linchuan Gan  1 , Baoxia Li  1 , Xue Su  1 , Baojia Huang  1 , Chen Xiao  1 , Ruijuan Zhu  1 , Guozhen Zhao  1 , Canshan Lao  1 , Chuan-Sheng Lin  1 , Dongya Zhang  1 , Xianzhi Jiang  1
Affiliations

Live biotherapeutic enterococcus lactis MNC-168 promotes the efficacy of immune checkpoint blockade in cancer therapy by activating STING pathway via bacterial membrane vesicles

Yibo Xian et al. Gut Microbes. 2025 Dec.

Abstract

The gut microbiome has the potential to influence tumor development and affect the efficacy of cancer therapeutics, particularly immunotherapy. However, the specific species and strains rather than all microbes that promote antitumor immunity by modulating the function of systemic immunity or tumor-infiltrating lymphocytes (TILs) in tumor environments remain to be elucidated. In this study, we analyzed the microbiome composition of responders and non-responders to PD-1 blockade therapy from a clinical cohort and found that Enterococcus spp. were abundant in the responders. Through in vitro screening, we identified Enterococcus lactis MNC-168, a commensal bacterium isolated from a healthy individual, which significantly inhibited tumor growth and enhanced the efficacy of anti-PD-1 treatment by promoting antitumor immunity. Mechanistically, MNC-168 activates innate immunity through a STING-IFN-I (stimulator of interferon genes-type I interferons) dependent pathway by releasing bacterial membrane vesicles (MVs), and targeting tumor tissue, thereby augmenting the antitumor immune response. Furthermore, we have confirmed the safety profile of MNC-168 and its enhancing effect on Anti-PD-1 activity across multiple preclinical models, as well as its potential clinical relevance to Anti-PD-1 therapy. These findings suggest that MNC-168 could represent a promising strategy for cancer therapy and has the potential to improve the efficacy of current immunotherapies.

Keywords: Enterococcus lactis; MNC-168; STING; bacterial membrane vesicles; immune system; immunotherapy.

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Conflict of interest statement

No potential conflict of interest was reported by the author(s).

Figures

Figure 1.
Figure 1.
MNC-168 inhibits tumor growth and enhances anti-PD-1 therapy.
Figure 2.
Figure 2.
MNC-168 activates systemic immune response and enhances T cell anti-tumor immunity in vivo. a.
Figure 3.
Figure 3.
MNC-168 induces type I IFN response via STING pathway to promote anti-tumor immunity. a.
Figure 4.
Figure 4.
MNC-168 triggers STING dependent anti-tumor immunity via secreted MVs.
Figure 5.
Figure 5.
MNC-168 enhances anti-PD-1 efficacy in various preclinical tumor models and clinical ICB treatment.
See this image and copyright information in PMC

References

    1. Rooks MG, Garrett WS.. Gut microbiota, metabolites and host immunity. Nat Rev Immunol. 2016;16(6):341–27. doi: 10.1038/nri.2016.42. - DOI - PMC - PubMed
    1. Smith K, McCoy KD, Macpherson AJ. Use of axenic animals in studying the adaptation of mammals to their commensal intestinal microbiota. Semin Immunol. 2007;19(2):59–69. doi: 10.1016/j.smim.2006.10.002. - DOI - PubMed
    1. Sekirov I, Tam NM, Jogova M, Robertson ML, Li Y, Lupp C, Finlay BB. Antibiotic-induced perturbations of the intestinal microbiota alter host susceptibility to enteric infection. Infect Immun. 2008;76(10):4726–4736. doi: 10.1128/IAI.00319-08. - DOI - PMC - PubMed
    1. Wu HJ, Ivanov II, Darce J, Hattori K, Shima T, Umesaki Y, Littman DR, Benoist C, Mathis D. Gut-residing segmented filamentous bacteria drive autoimmune arthritis via T helper 17 cells. Immunity. 2010;32(6):815–827. doi: 10.1016/j.immuni.2010.06.001. - DOI - PMC - PubMed
    1. Lathrop SK, Bloom SM, Rao SM, Nutsch K, Lio C-W, Santacruz N, Peterson DA, Stappenbeck TS, Hsieh C-S. Peripheral education of the immune system by colonic commensal microbiota. Nature. 2011;478(7368):250–254. doi: 10.1038/nature10434. - DOI - PMC - PubMed

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