肿瘤内微生物组的研究进展

doi:10.19401/j.cnki.1007-3639.2023.09.007

摘要/Abstract

摘要：

肿瘤内微生物组是指存在于肿瘤中并构成肿瘤微环境的微生物群体。虽然肿瘤病毒的研究已有百余年历史，但细菌、真菌等其他微生物在肿瘤中的存在现象及生物学意义却一直未有定论。近年来，随着高通量测序技术的发展，日益增多的证据表明，细菌等微生物确实能够存活于肿瘤组织中，并与肿瘤的发生、发展及耐药有一定的相关性。本文综述了肿瘤内微生物组的最新研究进展，总结了各肿瘤组织中微生物种群的特征及潜在功能，重点讨论了细菌微生物组在乳腺癌、胰腺癌和肺癌中的作用机制，并展望了其未来临床应用前景。

关键词: 癌, 肿瘤内微生物, 肿瘤免疫微环境, 宏基因组测序

Abstract:

Intratumoral microbiome is defined as the microbes that reside within tumor tissues to form the tumor microenvironment. Although substantial advances have been made in the research on virus infection and cancer during the past century, little is known about the existence and the role of intratumoral bacteria or fungi in cancer. In recent years, with the development of high-throughput sequencing technology, evidence has emerged to support the existence and functional activity of intratumoral bacteria. This review summarized the recent research progress in intratumoral microbiome, particularly their contribution to the carcinogenesis and chemoresistance of breast cancer, pancreatic cancer and lung cancer. The future perspectives of intratumoral microbiota in clinical application were also discussed.

Key words: Cancer, Intratumoral microbiome, Tumor immune microenvironment, Metagenome sequencing

中图分类号:

R730.3

李欣然, 梁依依, 屠红. 肿瘤内微生物组的研究进展[J]. 中国癌症杂志, 2023, 33(9): 866-873.

LI Xinran, LIANG Yiyi, TU Hong. Research progress of the intratumoral microbiome[J]. China Oncology, 2023, 33(9): 866-873.

图/表 1

表1

常见肿瘤中的微生物及其在肿瘤发生、发展中的作用和机制"

Cancer type	Microbial species	Function	Mechanism	Reference
Melanoma	Propionibacterium; Staphylococcus aureus; Corynebacterium	Promote cancer growth	Melanoma cells present HLA-conjugated intracellular bacterial peptides to activate T cell immune responses	[32-33]
Ovarian cancer	Proteobacteria; Firmicutes	Promote cancer growth and metastasis	Up-regulate the expression of TLR5 in tumor cells to promote the mobilization of MDSC; LPS up-regulates the expression of PI3K, EMT and metastasis-related genes in tumor cells	[34]
Nasopharyngeal carcinoma	Corynebacterium; Staphylococcus aureus	Promote cancer recurrence	The increase of bacteria in tumor is negatively correlated with tumor infiltration of CD8+ T cells	[35]
Brain glioma	Pseudomonas; Erythrobacillus; Actinomycetes	Promote cancer growth	Secretion of fatty acids, LPS and other metabolites through the brain-intestinal axis affects the central nervous system immunity	[36]
Bone tumour	Pseudomonas; Actinomycetes	Promote cancer growth	Degrade the hydroxyproline that makes up bone collagen	[3]
Colorectal cancer	Firmicutes; Bacteroidetes; Fusobacterium nucleatum	Promote cancer invasion and metastasis	Down-regulate the expression of m6A methyltransferase METTL3 in tumor tissue and enhance tumor invasiveness; CD8+ T cell infiltration in liver metastases is decreased and MDSC infiltration is increased to inhibit anti-tumor immune response	[3, 36]
Prostate cancer	Pseudomonas; Escherichia coli	Inhibit cancer metastasis and improve the efficacy of immunotherapy	Negatively associated with tumor metastasis; Enhance the immunogenicity of tumor cells; Increase tumor infiltration of immune effector cells	[37-38]
Gastric carcinoma	Peptostreptococcus Streptococcus; Fusobacterium nucleatum	Promote cancer growth or improve the efficacy of immunotherapy	Increase the content of N-nitrite compounds in the stomach and promote the colonization of harmful bacteria; Increase the expression of PD-L1 in gastric epithelial cells and induce T cell apoptosis; Up-regulate the purine metabolic pathway of the tumor flora, enhancing the immune response	[39-40]
Cutaneous T-cell lymphoma	Corynebacterium; Staphylococcus aureus	Promote cancer growth	Staphylococcal α-toxin induces normal cell death, while tumor cells are resistant; Inhibition of T cell killing promotes tumor immune escape	[41-42]
Oral squamous cell carcinoma	Fusobacterium nucleatum; Monad; Prevotella copri	Promote cancer growth and invasion	LPS promotes the release of IL-1 and VEGF in tumor and mononuclear cells and enhances tumor invasiveness; Bacterial metabolites such as acetaldehyde cause DNA damage and over proliferation of epithelial cells	[43]
Squamous cell carcinoma of head and neck	Fusobacterium; Staphylococcus aureus	Promote chronic inflammation; Promote cancer invasion	The amount of bacteria is positively correlated with the tumor infiltration of macrophages and promotes the inflammatory tumor microenvironment; Up-regulate EMT-related signaling molecules in tumor cells	[44-45]
Esophagus cancer	Fusobacterium; Proteobacteria	Promote cancer occurrence	LPS promotes cancer by promoting the release of inflammation-related mediators	[46]
Gallbladder cancer	Campylobacter; Phyllobacterium	Associated with survival and lymph node metastasis	Not involved	[47]
Bladder cancer	Staphylococcus aureus; Corynebacterium	Promote cancer progression and recurrence	Up-regulate the expression of PD-L1 in cancer tissues and promote immune escape	[48]
Cervical cancer	Lactobacillus; Fusobacterium	Promote cancer growth	Promote Th cells to secrete IL-1β, IL-6 and IL-8 to promote inflammation and inhibit anti-tumor immune response; Induce the accumulation of sphinolipids and glycerols in the outer membrane of cervical epithelial cells, leading to cell damage and the formation of pro-inflammatory microenvironment	[49-50]
Endometrial cancer	Porphyromonas; Bacteroides; Bacillus faecalis	Induce and promote cancer growth	Activate endometrial cells to produce pro-inflammatory cytokines; Release toxins that damage host DNA and induce autophagy and carcinogenesis	[51-52]

表1

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