Research progress on the role of intratumoral microbiota in colorectal cancer

doi:10.3877/cma.j.issn.2095-3224.2025.04.010

Abstract

Abstract:

Microorganisms are ubiquitously present in various human organs and play a significant role in the occurrence and development of colorectal cancer. While the gut microbiota has been extensively studied, knowledge about the intratumoral microbiota remains limited. Emerging evidence suggests that the intratumoral microbiota plays a critical role in shaping the tumor microenvironment, particularly in colorectal cancer. These microbes not only contribute to tumor initiation, progression, and metastasis but also modulate therapeutic responses. This review summarizes the current understanding of the intratumoral microbiota in colorectal cancer and its potential implications for enhancing cancer treatment outcomes.

Key words: Colorectal cancer, Intratumoral microbiota, Tumor treatment

Qianyu Wang, Hanchuan Guo, Bin Wu. Research progress on the role of intratumoral microbiota in colorectal cancer[J]. Chinese Journal of Colorectal Diseases(Electronic Edition), 2025, 14(04): 370-374.

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References 51

[1]	Han B, Zheng R, Zeng H, et al. Cancer incidence and mortality in China, 2022 [J]. J Natl Cancer Cent, 2024, 4(1): 47-53.
[2]	张金珠，杨明，王锡山. 中国、美国及世界结直肠癌流行病学与疾病负担的对比和思考[J]. 中华结直肠疾病电子杂志, 2024, 13(2): 89-93.
[3]	Wang Q, Shen X, Chen G, et al. Drug resistance in colorectal cancer: from mechanism to clinic[J]. Cancers (Basel), 2022, 14(12): 2928.
[4]	Li S, Yu W, Xie F, et al. Neoadjuvant therapy with immune checkpoint blockade, antiangiogenesis, and chemotherapy for locally advanced gastric cancer [J]. Nat Commun, 2023, 14(1): 8.
[5]	Blake SJ, Wolf Y, Boursi B, et al. Role of the microbiota in response to and recovery from cancer therapy [J]. Nat Rev Immunol, 2023, 24(5): 308-325.
[6]	Ferrari V, Rescigno M. The intratumoral microbiota: friend or foe?[J]. Trends Cancer, 2023, 9(6): 472-479.
[7]	Xue C, Chu Q, Zheng Q, et al. Current understanding of the intratumoral microbiome in various tumors [J]. Cell Rep Med, 2023, 4(1): 100884.
[8]	Mouradov D, Greenfield P, Li S, et al. Oncomicrobial community profiling identifies clinicomolecular and prognostic subtypes of colorectal cancer[J]. Gastroenterology, 2023, 165(1): 104-120.
[9]	Wang N, Fang JY. Fusobacterium nucleatum, a key pathogenic factor and microbial biomarker for colorectal cancer[J]. Trends Microbiol, 2023, 31(2): 159-172.
[10]	Rubinstein MR, Wang X, Liu W, et al. Fusobacterium nucleatum promotes colorectal carcinogenesis by modulating E-cadherin/β-catenin signaling via its FadA adhesin[J]. Cell Host Microbe, 2013, 14(2): 195-206.
[11]	Yang Y, Weng W, Peng J, et al. Fusobacterium nucleatum increases proliferation of colorectal cancer cells and tumor development in mice by activating toll-like receptor 4 signaling to nuclear factor-κB, and up-regulating expression of microRNA-21[J]. Gastroenterology, 2017, 152(4): 851-866.e24.
[12]	Zhang Y, Zhang L, Zheng S, et al. Fusobacterium nucleatum promotes colorectal cancer cells adhesion to endothelial cells and facilitates extravasation and metastasis by inducing ALPK1/NF-κB/ICAM1 axis[J]. Gut Microbes, 2022, 14(1): 2038852.
[13]	Chen S, Zhang L, Li M, et al. Fusobacterium nucleatum reduces METTL3-mediated m6A modification and contributes to colorectal cancer metastasis[J]. Nat Commun, 2022, 13(1): 1248.
[14]	Bertocchi A, Carloni S, Ravenda PS, et al. Gut vascular barrier impairment leads to intestinal bacteria dissemination and colorectal cancer metastasis to liver[J]. Cancer Cell, 2021, 39(5): 708-724.
[15]	Jans M, Kolata M, Blancke G, et al. Colibactin-driven colon cancer requires adhesin-mediated epithelial binding[J]. Nature, 2024, 635(8038): 472-480.
[16]	Zhang X, Yu D, Wu D, et al. Tissue-resident lachnospiraceae family bacteria protect against colorectal carcinogenesis by promoting tumor immune surveillance[J]. Cell Host Microbe, 2023, 31(3): 418-432.
[17]	LaCourse KD, Zepeda-Rivera M, Kempchinsky AG, et al. The cancer chemotherapeutic 5-fluorouracil is a potent Fusobacterium nucleatum inhibitor and its activity is modified by intratumoral microbiota[J]. Cell Rep, 2022, 41(7): 111625.
[18]	Serna G, Ruiz-Pace F, Hernando J, et al. Fusobacterium nucleatum persistence and risk of recurrence after preoperative treatment in locally advanced rectal cancer[J]. Ann Oncol, 2020, 31(10): 1366-1375.
[19]	Yu T, Guo F, Yu Y, et al. Fusobacterium nucleatum promotes chemoresistance to colorectal cancer by modulating autophagy[J]. Cell, 2017, 170(3): 548-563.
[20]	de Oliveira Alves N, Dalmasso G, Nikitina D, et al. The colibactin-producing Escherichia coli alters the tumor microenvironment to immunosuppressive lipid overload facilitating colorectal cancer progression and chemoresistance[J]. Gut Microbes, 2024, 16(1): 2320291.
[21]	Iida N, Dzutsev A, Stewart CA, et al. Commensal bacteria control cancer response to therapy by modulating the tumor microenvironment[J]. Science, 2013, 342(6161): 967-970.
[22]	Geller LT, Barzily-Rokni M, Danino T, et al. Potential role of intratumor bacteria in mediating tumor resistance to the chemotherapeutic drug gemcitabine[J]. Science, 2017, 357(6356): 1156-1160.
[23]	Spanogiannopoulos P, Kyaw TS, Guthrie BGH, et al. Host and gut bacteria share metabolic pathways for anti-cancer drug metabolism[J]. Nat Microbiol, 2022, 7(10):1605-1620.
[24]	Lehouritis P, Cummins J, Stanton M, et al. Local bacteria affect the efficacy of chemotherapeutic drugs[J]. Sci Rep, 2015, 5:14554.
[25]	Huang X, Chen C, Xie W, et al. Metagenomic analysis of intratumoral microbiome linking to response to neoadjuvant chemoradiotherapy in rectal cancer[J]. Int J Radiat Oncol Biol Phys, 2023, 117(5): 1255-1269.
[26]	Wang Q, Shen X, Chen G, et al. How to overcome resistance to immune checkpoint inhibitors in colorectal cancer: from mechanisms to translation[J]. Int J Cancer, 2023, 153(4): 709-722.
[27]	Gopalakrishnan V, Spencer CN, Nezi L, et al. Gut microbiome modulates response to anti-PD-1 immunotherapy in melanoma patients[J]. Science, 2018, 359(6371): 97-103.
[28]	Routy B, Le Chatelier E, Derosa L, et al. Gut microbiome influences efficacy of PD-1-based immunotherapy against epithelial tumors[J]. Science, 2018, 359(6371): 91-97.
[29]	Vétizou M, Pitt J M, Daillère R, et al. Anticancer immunotherapy by CTLA-4 blockade relies on the gut microbiota[J]. Science, 2015, 350(6264): 1079-1084.
[30]	Gopalakrishnan V, Spencer C, Reuben A, et al. Association of diversity and composition of the gut microbiome with differential responses to PD-1 based therapy in patients with metastatic melanoma[J]. Journal of Clinical Oncology, 2017, 35(7_suppl): 2.
[31]	Li W, Deng Y, Chu Q, et al. Gut microbiome and cancer immunotherapy[J]. Cancer Lett, 2019, 447: 41-47.
[32]	Gur C, Ibrahim Y, Isaacson B, et al. Binding of the Fap2 protein of Fusobacterium nucleatum to human inhibitory receptor TIGIT protects tumors from immune cell attack[J]. Immunity, 2015, 42(2): 344-355.
[33]	Borowsky J, Haruki K, Lau MC, et al. Association of Fusobacterium nucleatum with specific T-cell subsets in the colorectal carcinoma microenvironment[J]. Clin Cancer Res, 2021, 27(10): 2816-2826.
[34]	Gao Y, Bi D, Xie R, et al. Fusobacterium nucleatum enhances the efficacy of PD-L1 blockade in colorectal cancer[J]. Signal Transduct Target Ther, 2021, 6(1): 398.
[35]	Tahara T, Yamamoto E, Suzuki H, et al. Fusobacterium in colonic flora and molecular features of colorectal carcinoma[J]. Cancer Res, 2014, 74(5): 1311-1318.
[36]	Hamada T, Zhang X, Mima K, et al. Fusobacterium nucleatum in colorectal cancer relates to immune response differentially by tumor microsatellite instability status[J]. Cancer Immunol Res, 2018, 6(11): 1327-1336.
[37]	Park HE, Kim JH, Cho NY, et al. Intratumoral Fusobacterium nucleatum abundance correlates with macrophage infiltration and CDKN2A methylation in microsatellite-unstable colorectal carcinoma[J]. Virchows Arch, 2017, 471(3): 329-336.
[38]	Lin Y, Fan L, Qi Y, et al. Bifidobacterium adolescentis induces Decorin+ macrophages via TLR2 to suppress colorectal carcinogenesis[J]. J Exp Clin Cancer Res, 2023, 42(1): 172.
[39]	Overacre-Delgoffe AE, Bumgarner HJ, Cillo AR, et al. Microbiota-specific T follicular helper cells drive tertiary lymphoid structures and anti-tumor immunity against colorectal cancer[J]. Immunity, 2021, 54(12):2812-2824.
[40]	Xing C, Wang M, Ajibade AA, et al. Microbiota regulate innate immune signaling and protective immunity against cancer[J]. Cell Host Microbe, 2021, 29(6):959-974.
[41]	Yamamoto S, Kinugasa H, Hirai M, et al. Heterogeneous distribution of Fusobacterium nucleatum in the progression of colorectal cancer[J]. J Gastroenterol Hepatol, 2021, 36(7): 1869-1876.
[42]	Bullman S, Pedamallu CS, Sicinska E, et al. Analysis of Fusobacterium persistence and antibiotic response in colorectal cancer[J]. Science, 2017, 358(6369): 1443-1438.
[43]	Kosumi K, Hamada T, Koh H, et al. The amount of bifidobacterium genus in colorectal carcinoma tissue in relation to tumor characteristics and clinical outcome[J]. Am J Pathol, 2018, 188(12): 2839-2852.
[44]	Liu W, Zhang X, Xu H, et al. Microbial community heterogeneity within colorectal neoplasia and its correlation with colorectal carcinogenesis[J]. Gastroenterology, 2021, 160(7): 2395-2408.
[45]	Murphy CL, Barrett M, Pellanda P, et al. Mapping the colorectal tumor microbiota[J]. Gut Microbes, 2021, 13(1):1-10.
[46]	Flemer B, Lynch DB, Brown JMR, et al. Tumour-associated and non-tumour-associated microbiota in colorectal cancer[J]. Gut, 2017, 66(4): 633-643.
[47]	Alexander JL, Posma JM, Scott A, et al. Pathobionts in the tumour microbiota predict survival following resection for colorectal cancer[J]. Microbiome, 2023, 11(1): 100.
[48]	Chen L, Zhao R, Shen J, et al. Antibacterial fusobacterium nucleatum-mimicking nanomedicine to selectively eliminate tumor-colonized bacteria and enhance immunotherapy against colorectal cancer[J]. Adv Mater, 2023, 35(45): e2306281.
[49]	Chen L, Kang Z, Shen J, et al. An emerging antibacterial nanovaccine for enhanced chemotherapy by selectively eliminating tumor-colonizing bacteria[J]. Sci Bull (Beijing), 2024, 69(16):2565-2579.
[50]	Gao G, Jiang YW, Chen J, et al. Three-in-one peptide prodrug with targeting, assembly and release properties for overcoming bacterium-induced drug resistance and potentiating anti-cancer immune response[J]. Adv Mater, 2024, 36(23): e2312153.
[51]	Gardner HA, Kashyap S, Ponichtera H, et al. Monoclonal microbial EDP1503 to induce antitumor responses via gut-mediated activation of both innate and adaptive immunity[J]. Journal of Clinical Oncology, 2019, 37(15_suppl): e14241.

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