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Original Article | Open Access

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

Chengyi Li1,2,*, Xuehua Zhang3,*, Yichen Yang4,*, Haotian Zeng1,2,*, Yanqiang Shi1,2, Jinjin Zhang1,2, Lingjun Liu1,2, Chenwei Zhu1,2, Zhiwen Zhang1,2, Chao Li1,2, Xudong Wang5, Xiaowu Bai3, Haijun Deng3 ( ), Qing Li1,2 ( )
Dermatology Hospital, Southern Medical University, Guangzhou 510515, China
The First School of Clinical Medicine, Southern Medical University, Guangzhou 510515, China
Department of General Surgery, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China
Department of Anaesthesia and Intensive Care and Peter Hung Pain Research Institute, The Chinese University of Hong Kong, Hong Kong SAR, China
State Key Laboratory of Applied Microbiology Southern China, Institute of Microbiology, Guangdong Academy of Sciences, Guangzhou 510515, China

*These authors contributed equally to this work.

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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 animalismelanomamannoseCD8+ T cellsanti-PD-1

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Cancer Biology & Medicine
Volume 23 Issue 5,
May 2026
Pages 737-754
DOI: 10.20892/j.issn.2095-3941.2025.0652

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Cite this article:
Li C, Zhang X, Yang Y, et al. Bifidobacterium animalis suppresses melanoma progression and activates anti-tumor immunity by inhibiting YAP1 expression in CD8+ T cells. Cancer Biology & Medicine, 2026, 23(5): 737-754. https://doi.org/10.20892/j.issn.2095-3941.2025.0652

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Received: 22 October 2025
Accepted: 27 February 2026
Published: 06 May 2026
©2026 The Authors.

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