2. Academic Validation
  3. Alistipes finegoldii augments the efficacy of immunotherapy against solid tumors

Alistipes finegoldii augments the efficacy of immunotherapy against solid tumors

  • Cancer Cell. 2025 Sep 8;43(9):1714-1730.e12. doi: 10.1016/j.ccell.2025.07.002.
Zhi-Ying Wu 1,  Qi-Wen Wu 1,  Yi Han 2,  Shu-Jing Xiang 3,  Ying-Nan Wang 1,  Wen-Wei Wu 1,  Yan-Xing Chen 3,  Zi-Qing Feng 1,  Yi-Yu Wang 1,  Ze-Gong Xu 4,  Huan-Chun He 4,  Jun-Jie He 5,  Jia-Qi Chen 4,  Hui Sheng 6,  Qi-Hua Zhang 6,  Zi-Xian Wang 1,  Kun Liao 6,  Qi Zhao 7,  Wei-Jian Mei 8,  Pei-Rong Ding 8,  Miao-Zhen Qiu 1,  Feng Wang 1,  Huai-Qiang Ju 4,  Hui-Yan Luo 1,  Xia Zhao 9,  Rui-Hua Xu 10
Affiliations

Affiliations

  • 1 Department of Medical Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University, Guangzhou 510060, P.R. China; Research Unit of Precision Diagnosis and Treatment for Gastrointestinal Cancer, Chinese Academy of Medical Sciences, Guangzhou 510060, P.R. China.
  • 2 Research Unit of Precision Diagnosis and Treatment for Gastrointestinal Cancer, Chinese Academy of Medical Sciences, Guangzhou 510060, P.R. China; Cancer Microbiome Platform, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Sun Yat-sen University, Guangzhou 510060, China.
  • 3 Department of Medical Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University, Guangzhou 510060, P.R. China; Research Unit of Precision Diagnosis and Treatment for Gastrointestinal Cancer, Chinese Academy of Medical Sciences, Guangzhou 510060, P.R. China; Bioinformatics Platform, Sun Yat-sen University Cancer Center, Guangzhou 510060, P.R. China.
  • 4 Research Unit of Precision Diagnosis and Treatment for Gastrointestinal Cancer, Chinese Academy of Medical Sciences, Guangzhou 510060, P.R. China; Department of Experimental Research, Sun Yat-sen University Cancer Center, Guangzhou 510060, P.R. China.
  • 5 Research Unit of Precision Diagnosis and Treatment for Gastrointestinal Cancer, Chinese Academy of Medical Sciences, Guangzhou 510060, P.R. China; Department of Experimental Research, Sun Yat-sen University Cancer Center, Guangzhou 510060, P.R. China; Cancer Microbiome Platform, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Sun Yat-sen University, Guangzhou 510060, China.
  • 6 Research Unit of Precision Diagnosis and Treatment for Gastrointestinal Cancer, Chinese Academy of Medical Sciences, Guangzhou 510060, P.R. China.
  • 7 Research Unit of Precision Diagnosis and Treatment for Gastrointestinal Cancer, Chinese Academy of Medical Sciences, Guangzhou 510060, P.R. China; Bioinformatics Platform, Sun Yat-sen University Cancer Center, Guangzhou 510060, P.R. China; Department of Experimental Research, Sun Yat-sen University Cancer Center, Guangzhou 510060, P.R. China; Cancer Microbiome Platform, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Sun Yat-sen University, Guangzhou 510060, China.
  • 8 Department of Colorectal Surgery, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Sun Yat-sen University, Guangzhou 510060, P.R. China.
  • 9 Research Unit of Precision Diagnosis and Treatment for Gastrointestinal Cancer, Chinese Academy of Medical Sciences, Guangzhou 510060, P.R. China; Department of Microbiology, Army Medical University, Chongqing 400038, P.R. China; Cancer Microbiome Platform, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Sun Yat-sen University, Guangzhou 510060, China. Electronic address: zhaoxia413@163.com.
  • 10 Department of Medical Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University, Guangzhou 510060, P.R. China; Research Unit of Precision Diagnosis and Treatment for Gastrointestinal Cancer, Chinese Academy of Medical Sciences, Guangzhou 510060, P.R. China. Electronic address: xurh@sysucc.org.cn.
PMID: 40712567 DOI: 10.1016/j.ccell.2025.07.002
Abstract

The emergence of immunotherapy has revolutionized Cancer therapy. However, immunotherapeutic resistance remains a major obstacle for broader clinical application. Recent studies highlight that gut microbiota enhances immunotherapy by modulating anti-tumor immunity. In our investigation, we identify that Alistipes finegoldii (A. finegoldii) is associated with superior immunotherapy efficacy across multiple cohorts. Subsequent in vitro and in vivo experiments reveal that A. finegoldii enhances CD8+ T cell chemotaxis via the CXCL16-CXCR6 axis, enhancing immunotherapy efficacy. Mechanistically, a lipoprotein derived from A. finegoldii (LIPOAF) activates the nuclear factor kappa B (NF-κB) signaling pathway to augment CXCL16 expression in CCR7+ conventional dendritic cells through binding with the Toll-like Receptor 2. Released CXCL16 subsequently facilitates the recruitment of CXCR6+CD8+ T cells into the tumor microenvironment, effectively curbing tumor growth. Our findings suggest a promising strategy for treating solid tumors by combining A. finegoldii with immunotherapy.

Keywords

Alistipes finegoldii; CXCL16; CXCR6; TLR2; anti-tumor immunity; gut microbiome; immunotherapy; lipoprotein; solid tumor.

Figures
Products
Inhibitors & Agonists
Other Products