Bifidobacterium animalis suppresses melanoma progression and activates anti-tumor immunity by inhibiting YAP1 expression in CD8+ T cells

Chengyi Li; Xuehua Zhang; Yichen Yang; Haotian Zeng; Yanqiang Shi; Jinjin Zhang; Lingjun Liu; Chenwei Zhu; Zhiwen Zhang; Chao Li; Xudong Wang; Xiaowu Bai; Haijun Deng; Qing Li

doi:10.20892/j.issn.2095-3941.2025.0652

Bifidobacterium animalis suppresses melanoma progression and activates anti-tumor immunity by inhibiting YAP1 expression in CD8+ T cells

Cancer Biol Med. 2026 May 6;23(5):737-754. doi: 10.20892/j.issn.2095-3941.2025.0652.

Authors

Chengyi Li^#^{1

2}, Xuehua Zhang^#³, Yichen Yang^#⁴, Haotian Zeng^#^{1

2}, Yanqiang Shi^{1

2}, Jinjin Zhang^{1

2}, Lingjun Liu^{1

2}, Chenwei Zhu^{1

2}, Zhiwen Zhang^{1

2}, Chao Li^{1

2}, Xudong Wang⁵, Xiaowu Bai³, Haijun Deng³, Qing Li^{1

2}

Affiliations

¹ Dermatology Hospital, Southern Medical University, Guangzhou 510515, China.
² The First School of Clinical Medicine, Southern Medical University, Guangzhou 510515, China.
³ Department of General Surgery, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
⁴ Department of Anaesthesia and Intensive Care and Peter Hung Pain Research Institute, The Chinese University of Hong Kong, Hong Kong SAR, China.
⁵ State Key Laboratory of Applied Microbiology Southern China, Institute of Microbiology, Guangdong Academy of Sciences, Guangzhou 510515, China.

^# Contributed equally.

PMID: 42093272
PMCID: PMC13244316
DOI: 10.20892/j.issn.2095-3941.2025.0652

Abstract

Objective: The probiotic, Bifidobacterium animalis, (B. animalis) is known to provide health benefits in humans. This study investigated the role of B. animalis in suppressing malignant melanoma progression and modulating tumor immunity.

Methods: Bifidobacterium spp. were isolated from human faeces and verified by whole-genome sequencing. The anti-tumor effects were assessed in B16-F10 melanoma cells. B. animalis efficacy was further evaluated in a syngeneic murine model. Immune profiling was performed with flow cytometry and CD8⁺ T cell dependency was tested with antibody depletion. Functional metabolites were analyzed by liquid chromatography-mass spectrometry (LC-MS). Transcriptome sequencing elucidated the YAP1 mechanism in CD8⁺ T cells. Gut microbiota composition was assessed via shotgun metagenomic sequencing.

Results: Among the selected Bifidobacterium spp., B. animalis and its conditioned medium effectively inhibited melanoma cell proliferation. Oral administration of B. animalis significantly reduced the growth of B16-F10 allografts, accompanied by an increase in tumor-infiltrating effector T cells. The bioactive component of B. animalis was identified as a < 3-kDa non-protein fraction containing mannose, which phenocopied the anti-tumor and immunostimulatory effects of B. animalis. Microbiota profiling revealed probiotic enrichment in mannose-treated mice. CD8⁺ T cell depletion abrogated mannose efficacy. Combination therapy with B. animalis and anti-PD-1 synergistically enhanced tumor control and T cell activation. Mechanistically, the bioactive fraction and mannose downregulated YAP1 expression in CD8⁺ T cells.

Conclusions: B. animalis suppresses melanoma tumorigenesis in mice by restoring gut microbiota and secreting functional mannose. Mannose enhances anti-PD-1 efficacy by inhibiting YAP1 expression in CD8⁺ T cells, thereby improving effector function. B. animalis may serve as a preventive measure for melanoma management.

Keywords: Bifidobacterium animalis; CD8⁺ T cells; anti-PD-1; mannose; melanoma.

Abstract

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