Lactobacillus intestinalis facilitates tumor-derived CCL5 to recruit dendritic cell and suppress colorectal tumorigenesis

Yong Sun; Qiwen Wang; Yao Jiang; Jiamin He; Dingjiacheng Jia; Man Luo; Wentao Shen; Qingyi Wang; Yadong Qi; Yifeng Lin; Ying Zhang; Lan Wang; Liangjing Wang; Shujie Chen; Lina Fan

doi:10.1080/19490976.2024.2449111

Lactobacillus intestinalis facilitates tumor-derived CCL5 to recruit dendritic cell and suppress colorectal tumorigenesis

Gut Microbes. 2025 Dec;17(1):2449111. doi: 10.1080/19490976.2024.2449111. Epub 2025 Jan 8.

Authors

Yong Sun^{1

2}, Qiwen Wang^{2

3}, Yao Jiang^{1

2}, Jiamin He^{2

3}, Dingjiacheng Jia^{1

2}, Man Luo⁴, Wentao Shen^{2

3}, Qingyi Wang^{2

3}, Yadong Qi^{2

3}, Yifeng Lin^{1

2}, Ying Zhang^{1

2}, Lan Wang^{2

3}, Liangjing Wang^{1

2

5}, Shujie Chen^{2

3

5}, Lina Fan^{1

2}

Affiliations

¹ Department of Gastroenterology, Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China.
² Institution of Gastroenterology, Zhejiang University, Hangzhou, Zhejiang Province, China.
³ Department of Gastroenterology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China.
⁴ Department of Nutrition, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China.
⁵ Prevention and Treatment Research Center of Senescent Disease, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China.

Abstract

Gut microbes play a crucial role in regulating the tumor microenvironment (TME) of colorectal cancer (CRC). Nevertheless, the deep mechanism between the microbiota-TME interaction has not been well explored. In this study, we for the first time discovered that Lactobacillus intestinalis (L. intestinalis) effectively suppressed tumor growth both in the AOM/DSS-induced CRC model and the Apc^Min/+ spontaneous adenoma model. Our investigation revealed that L. intestinalis increased the infiltration of immune cells, particularly dendritic cells (DC), in the TME. Mechanically, the tumor-derived CCL5 induced by L. intestinalis recruited DC chemotaxis through the NOD1/NF-κB signaling pathway. In clinical samples and datasets, we found positive correlation between L. intestinalis, CCL5 level, and the DC-related genes. Our study provided a new strategy for microbial intervention for CRC and deepened the understanding of the interaction between tumor cells and the immune microenvironment modulated by gut microbes.

Keywords: CCL5; Lactobacillus intestinalis; NF-κB; colorectal cancer; dendritic cells.

MeSH terms

Animals
Carcinogenesis
Chemokine CCL5* / genetics
Chemokine CCL5* / metabolism
Colorectal Neoplasms* / immunology
Colorectal Neoplasms* / microbiology
Colorectal Neoplasms* / pathology
Dendritic Cells* / immunology
Gastrointestinal Microbiome*
Humans
Lactobacillus / physiology
Male
Mice
Mice, Inbred C57BL
NF-kappa B / genetics
NF-kappa B / metabolism
Nod1 Signaling Adaptor Protein / genetics
Nod1 Signaling Adaptor Protein / metabolism
Signal Transduction
Tumor Microenvironment* / immunology

Substances

Chemokine CCL5
NF-kappa B
Nod1 Signaling Adaptor Protein
Nod1 protein, mouse
Ccl5 protein, mouse

Grants and funding

This work was financially supported by the National Natural Science Foundation of China [grant no. 82203618, to L. Fan; grant no. 82273269, to L. Wang; grant no. 82303271, to Y. Zhang], Zhejiang Province Medicine and Health Science and Technology Project [grant no. 2023KY722, to L. Fan], Natural Science Foundation Joint Fund Project of Zhejiang Province [grant no. LHDMD24H160001 to S. Chen], and Beijing CSCO Clinical Oncology Research Foundation [grant no. Y-NESTLE2022ZD—0195 to M. Luo].