The enrichment of the gut microbiota Lachnoclostridium is associated with the presence of intratumoral tertiary lymphoid structures in hepatocellular carcinoma

Rui Zhao; Jiacheng Li; Bo Chen; Jungang Zhao; Leyin Hu; Kate Huang; Qiwen Chen; Jiangqiao Yao; Ganglian Lin; Lishimeng Bao; Mengmeng Lu; Yi Wang; Gang Chen; Fang Wu

doi:10.3389/fimmu.2023.1289753

The enrichment of the gut microbiota Lachnoclostridium is associated with the presence of intratumoral tertiary lymphoid structures in hepatocellular carcinoma

Front Immunol. 2023 Dec 5:14:1289753. doi: 10.3389/fimmu.2023.1289753. eCollection 2023.

Authors

Rui Zhao^#¹, Jiacheng Li^#², Bo Chen^#², Jungang Zhao², Leyin Hu³, Kate Huang³, Qiwen Chen¹, Jiangqiao Yao², Ganglian Lin², Lishimeng Bao⁴, Mengmeng Lu¹, Yi Wang^{5

6}, Gang Chen^{2

6

7}, Fang Wu¹

Affiliations

¹ Department of Gastroenterology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
² Department of Hepatobiliary Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
³ Department of Pathology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
⁴ The Second Clinical College, Wenzhou Medical University, Wenzhou, China.
⁵ Department of Epidemiology and Biostatistics, School of Public Health and Management, Wenzhou Medical University, Wenzhou, China.
⁶ Zhejiang-Germany Interdisciplinary Joint Laboratory of Hepatobiliary-Pancreatic Tumor and Bioengineering, Wenzhou, China.
⁷ Key Laboratory of Diagnosis and Treatment of Severe Hepato-Pancreatic Diseases of Zhejiang Province, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.

^# Contributed equally.

Abstract

Backgrounds and aims: Immunotherapies have formed an entirely new treatment paradigm for hepatocellular carcinoma (HCC). Tertiary lymphoid structure (TLS) has been associated with good response to immunotherapy in most solid tumors. Nonetheless, the role of TLS in human HCC remains controversial, and recent studies suggest that their functional heterogeneity may relate to different locations within the tumor. Exploring factors that influence the formation of TLS in HCC may provide more useful insights. However, factors affecting the presence of TLSs are still unclear. The human gut microbiota can regulate the host immune system and is associated with the efficacy of immunotherapy but, in HCC, whether the gut microbiota is related to the presence of TLS still lacks sufficient evidence.

Methods: We performed pathological examinations of tumor and para-tumor tissue sections. Based on the location of TLS in tissues, all patients were divided into intratumoral TLS (It-TLS) group and desertic TLS (De-TLS) group. According to the grouping results, we statistically analyzed the clinical, biological, and pathological features; preoperative gut microbiota data; and postoperative pathological features of patients.

Results: In a retrospective study cohort of 60 cases from a single center, differential microbiota analysis showed that compared with the De-TLS group, the abundance of Lachnoclostridium, Hungatella, Blautia, Fusobacterium, and Clostridium was increased in the It-TLS group. Among them, the enrichment of Lachnoclostridium was the most significant and was unrelated to the clinical, biological, and pathological features of the patients. It can be seen that the difference in abundance levels of microbiota is related to the presence of TLS.

Conclusion: Our findings prove the enrichment of Lachnoclostridium-dominated gut microbiota is associated with the presence of It-TLS in HCC patients.

Keywords: Lachnoclostridium; gut microbiota; hepatocellular carcinoma (HCC); tertiary lymphoid structure (TLS); tumor immune microenvironment (TIME).

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Carcinoma, Hepatocellular* / therapy
Clostridiales
Gastrointestinal Microbiome*
Humans
Liver Neoplasms* / therapy
Retrospective Studies
Tertiary Lymphoid Structures*

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This study was supported by National Natural Science Foundation of China (Grant numbers: 82072685), Huadong Medicine Joint Funds of the Zhejiang Provincial Natural Science Foundation of China under Grant No. LHDMY23H100001.