2. Academic Validation
  3. Tumor-colonized Streptococcus mutans metabolically reprograms tumor microenvironment and promotes oral squamous cell carcinoma

Tumor-colonized Streptococcus mutans metabolically reprograms tumor microenvironment and promotes oral squamous cell carcinoma

  • Microbiome. 2024 Oct 5;12(1):193. doi: 10.1186/s40168-024-01907-9.
Jiaying Zhou # 1 2,  Zixuan Hu # 3 4 5,  Lei Wang # 6 7 8,  Qinchao Hu # 1 2,  Zixu Chen # 9,  Tao Lin 9,  Rui Zhou 1 2,  Yongjie Cai 9,  Zhiying Wu 9,  Zhiyi Zhang 9,  Yi Yang 9,  Cuijuan Zhang 10,  Guibo Li 6 7 8,  Lingchan Zeng 1,  Kai Su 1 2,  Huan Li 11,  Qiao Su 12,  Gucheng Zeng 13,  Bin Cheng 14 15,  Tong Wu 16 17
Affiliations

Affiliations

  • 1 Hospital of Stomatology, Guanghua School of Stomatology, Sun Yat-Sen University, 56 Lingyuan Road West, Guangzhou, 510055, China.
  • 2 Guangdong Provincial Key Laboratory of Stomatology, Guangzhou, 510080, China.
  • 3 The Affiliated Stomatological Hospital, Jiangxi Medical College, Nanchang University, Nanchang, 330006, China.
  • 4 Jiangxi Province Key Laboratory of Oral Biomedicine, Nanchang, 330006, China.
  • 5 Jiangxi Province Clinical Research Center for Oral Diseases, Nanchang, 330006, China.
  • 6 BGI Research, Chongqing, 401329, China.
  • 7 Guangdong Provincial Key Laboratory of Human Disease Genomics, BGI Research, Shenzhen, 518083, China.
  • 8 Shenzhen Key Laboratory of Single-Cell Omics, BGI Research, Shenzhen, 518083, China.
  • 9 Department of Microbiology, Key Laboratory for Tropical Diseases Control of the Ministry of Education, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, 510080, China.
  • 10 BGI Research, Shenzhen, 518083, China.
  • 11 Department of Intensive Care Unit (ICU), State Key Laboratory of Oncology in South China, CollaborativeInnovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, China.
  • 12 Animal Experiment Center, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, 510080, China.
  • 13 Department of Microbiology, Key Laboratory for Tropical Diseases Control of the Ministry of Education, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, 510080, China. zenggch@mail.sysu.edu.cn.
  • 14 Hospital of Stomatology, Guanghua School of Stomatology, Sun Yat-Sen University, 56 Lingyuan Road West, Guangzhou, 510055, China. chengbin@mail.sysu.edu.cn.
  • 15 Guangdong Provincial Key Laboratory of Stomatology, Guangzhou, 510080, China. chengbin@mail.sysu.edu.cn.
  • 16 Hospital of Stomatology, Guanghua School of Stomatology, Sun Yat-Sen University, 56 Lingyuan Road West, Guangzhou, 510055, China. wutong23@mail.sysu.edu.cn.
  • 17 Guangdong Provincial Key Laboratory of Stomatology, Guangzhou, 510080, China. wutong23@mail.sysu.edu.cn.
  • # Contributed equally.
PMID: 39369210 DOI: 10.1186/s40168-024-01907-9
Abstract

Background: Oral squamous cell carcinoma (OSCC) remains a major death cause in head and neck cancers, but the exact pathogenesis mechanisms of OSCC are largely unclear.

Results: Saliva derived from OSCC patients but not healthy controls (HCs) significantly promotes OSCC development and progression in rat models, and metabolomic analyses reveal saliva of OSCC patients but not HCs and OSCC tissues but not adjacent non-tumor tissues contain higher levels of kynurenic acid (KYNA). Furthermore, large amounts of Streptococcus mutans (S. mutans) colonize in OSCC tumor tissues, and such intratumoral S. mutans mediates KYNA overproductions via utilizing its protein antigen c (PAc). KYNA shifts the cellular types in the tumor microenvironment (TME) of OSCC and predominantly expedites the expansions of S100a8highS100a9high neutrophils to produce more interleukin 1β (IL-1β), which further expands neutrophils and induces CD8 + T cell exhaustion in TME and therefore promotes OSCC. Also, KYNA compromises the therapeutic effects of programmed cell death ligand 1 (PD-L1) and IL-1β blockades in oral carcinogenesis model. Moreover, KYNA-mediated immunosuppressive program and Aryl Hydrocarbon Receptor (AHR) expression correlate with impaired anti-tumor immunity and poorer survival of OSCC patients.

Conclusions: Thus, aberration of oral microbiota and intratumoral colonization of specific oral bacterium such as S. mutans may increase the production of onco-metabolites, exacerbate the oral mucosal carcinogenesis, reprogram a highly immunosuppressive TME, and promote OSCC, highlighting the potential of interfering with oral microbiota and microbial metabolism for OSCC preventions and therapeutics. Video Abstract.

Keywords

Oral microbiota; Oral squamous cell carcinoma; Tumor microenvironment.

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