Mechanism and research progress in intratumoral microbiota in the pathogenesis and progression of pancreatic cancer

doi:10.3877/cma.j.issn.2095-3232.2024.04.023

Abstract

Abstract:

Pancreatic cancer is one of the common malignant tumors in the digestive tract. Interstitial fibrosis and immunosuppression are the characteristics of the tumor microenvironment. Increasing studies have confirmed that unique microbial community exists in pancreatic cancer. Bacteria-based intratumoral microbiota can induce tumor inflammation, affect local immunity and regulate tumor metabolism in multiple ways, becoming an important part of tumor microenvironment. The quantity and composition of intratumoral microbiota play a critical role in the incidence and development of pancreatic cancer, and also affect clinical efficacy of chemotherapy and immunotherapy. The association between specific microbiota and pancreatic cancer enables intratumoral microbiota to have the potential to become novel diagnostic and prognostic biomarkers and possible therapeutic targets. In this article, the latest research progress in the composition, role and clinical application value of intratumoral microbiota in pancreatic cancer was reviewed, aiming to provide theoretical basis and useful reference for subsequent research.

Key words: Pancreatic cancer, Intratumoral microbe, Pathogenesis, Treatment

Yufan Meng, Yongzheng Li, Zhiyao Fan, Hanxiang Zhan. Mechanism and research progress in intratumoral microbiota in the pathogenesis and progression of pancreatic cancer[J]. Chinese Journal of Hepatic Surgery(Electronic Edition), 2024, 13(04): 577-582.

/ / Recommend

Add to citation manager EndNote|Ris|BibTeX

URL: https://zhgzwkssxdzzz.cma-cmc.com.cn/EN/10.3877/cma.j.issn.2095-3232.2024.04.023

https://zhgzwkssxdzzz.cma-cmc.com.cn/EN/Y2024/V13/I04/577

References 57

[1]	Siegel RL, Miller KD, Jemal A. Cancer statistics, 2015[J]. CA A Cancer J Clin, 2015, 65(1):5-29.
[2]	Xia C, Dong X, Li H, et al. Cancer statistics in China and United States, 2022: profiles, trends, and determinants[J]. Chin Med J, 2022, 135(5):584-590.
[3]	Jiang Z, Zhang W, Zhang Z, et al. Intratumoral microbiota: a new force in diagnosing and treating pancreatic cancer[J]. Cancer Lett, 2023, 554: 216031.
[4]	Huang Y, Zhu N, Zheng X, et al. Intratumor microbiome analysis identifies positive association between Megasphaera and survival of Chinese patients with pancreatic ductal adenocarcinomas[J]. Front Immunol, 2022, 13: 785422.
[5]	Riquelme E, Zhang Y, Zhang L, et al. Tumor microbiome diversity and composition influence pancreatic cancer outcomes[J]. Cell, 2019, 178(4):795-806, e12.
[6]	He Y, Zhang Q, Yu X, et al. Overview of microbial profiles in human hepatocellular carcinoma and adjacent nontumor tissues[J]. J Transl Med, 2023, 21(1):68.
[7]	Yuan L, Yang P, Wei G, et al. Tumor microbiome diversity influences papillary thyroid cancer invasion[J]. Commun Biol, 2022, 5(1):864.
[8]	Phipps O, Quraishi MN, Dickson EA, et al. Differences in the on- and off-tumor microbiota between right- and left-sided colorectal cancer[J]. Microorganisms, 2021, 9(5):1108.
[9]	Abdul Rahman R, Lamarca A, Hubner RA, et al. The microbiome as a potential target for therapeutic manipulation in pancreatic cancer[J]. Cancers, 2021, 13(15):3779.
[10]	Pfisterer N, Lingens C, Heuer C, et al. The microbiome in PDAC-vantage point for future therapies?[J]. Cancers, 2022, 14(23):5974.
[11]	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.
[12]	Nejman D, Livyatan I, Fuks G, et al. The human tumor microbiome is composed of tumor type-specific intracellular bacteria[J]. Science, 2020, 368(6494):973-980.
[13]	Pushalkar S, Hundeyin M, Daley D, et al. The pancreatic cancer microbiome promotes oncogenesis by induction of innate and adaptive immune suppression[J]. Cancer Discov, 2018, 8(4):403-416.
[14]	Tan Q, Ma X, Yang B, et al. Periodontitis pathogen Porphyromonas gingivalis promotes pancreatic tumorigenesis via neutrophil elastase from tumor-associated neutrophils[J]. Gut Microbes, 2022, 14(1):2073785.
[15]	Riquelme E, Zhang Y, Zhang L, et al. Tumor microbiome diversity and composition influence pancreatic cancer outcomes[J]. Cell, 2019, 178(4):795-806, e12.
[16]	Chakladar J, Kuo SZ, Castaneda G, et al. The pancreatic microbiome is associated with carcinogenesis and worse prognosis in males and smokers[J]. Cancers, 2020, 12(9):2672.
[17]	McKinley KNL, Herremans KM, Riner AN, et al. Translocation of oral microbiota into the pancreatic ductal adenocarcinoma tumor microenvironment[J]. Microorganisms, 2023, 11(6):1466.
[18]	Aykut B, Pushalkar S, Chen R, et al. The fungal mycobiome promotes pancreatic oncogenesis via activation of MBL[J]. Nature, 2019, 574(7777):264-267.
[19]	Chung LM, Liang JA, Lin CL, et al. Cancer risk in patients with candidiasis: a nationwide population-based cohort study[J]. Oncotarget, 2017, 8(38):63562-63573.
[20]	Poudel SK, Padmanabhan R, Dave H, et al. Microbiomic profiles of bile in patients with benign and malignant pancreaticobiliary disease[J]. PLoS One, 2023, 18(4):e0283021.
[21]	Kohi S, Macgregor-Das A, Dbouk M, et al. Alterations in the duodenal fluid microbiome of patients with pancreatic cancer[J]. Clin Gastroenterol Hepatol, 2022, 20(2):e196-227.
[22]	Gao F, Yu B, Rao B, et al. The effect of the intratumoral microbiome on tumor occurrence, progression, prognosis and treatment[J]. Front Immunol, 2022, 13:1051987.
[23]	Guo W, Zhang Y, Guo S, et al. Tumor microbiome contributes to an aggressive phenotype in the basal-like subtype of pancreatic cancer[J]. Commun Biol, 2021, 4(1):1019.
[24]	Ochi A, Nguyen AH, Bedrosian AS, et al. MyD88 inhibition amplifies dendritic cell capacity to promote pancreatic carcinogenesis via Th2 cells[J]. J Exp Med, 2012, 209(9):1671-1687.
[25]	Ochi A, Graffeo CS, Zambirinis CP, et al. Toll-like receptor 7 regulates pancreatic carcinogenesis in mice and humans[J]. J Clin Investig, 2012, 122(11):4118-4129.
[26]	Pandya G, Kirtonia A, Singh A, et al. A comprehensive review of the multifaceted role of the microbiota in human pancreatic carcinoma[J]. Semin Cancer Biol, 2022, 86(Pt 3):682-692.
[27]	Wei MY, Shi S, Liang C, et al. The microbiota and microbiome in pancreatic cancer: more influential than expected[J]. Mol Cancer, 2019, 18(1):97.
[28]	Öğrendik M. Periodontal pathogens in the etiology of pancreatic cancer[J]. Gastrointest Tumors, 2017, 3(3/4):125-127.
[29]	Kadosh E, Snir-Alkalay I, Venkatachalam A, et al. The gut microbiome switches mutant p53 from tumour-suppressive to oncogenic[J]. Nature, 2020, 586(7827):133-138.
[30]	Tintelnot J, Xu Y, Lesker TR, et al. Microbiota-derived 3-IAA influences chemotherapy efficacy in pancreatic cancer[J]. Nature, 2023, 615(7950):168-174.
[31]	Amara S, Yang LV, Tiriveedhi V, et al. Complex role of microbiome in pancreatic tumorigenesis: potential therapeutic implications[J]. Cells, 2022, 11(12):1900.
[32]	Nagathihalli NS, Beesetty Y, Lee W, et al. Novel mechanistic insights into ectodomain shedding of EGFR Ligands Amphiregulin and TGF-α: impact on gastrointestinal cancers driven by secondary bile acids[J]. Cancer Res, 2014, 74(7):2062-2072.
[33]	Yang Q, Wang B, Zheng Q, et al. A review of gut microbiota-derived metabolites in tumor progression and cancer therapy[J]. Adv Sci, 2023, 10(15):e2207366.
[34]	Hezaveh K, Shinde RS, Klötgen A, et al. Tryptophan-derived microbial metabolites activate the aryl hydrocarbon receptor in tumor-associated macrophages to suppress anti-tumor immunity[J]. Immunity, 2022, 55(2):324-340, e8.
[35]	Udayasuryan B, Ahmad RN, Nguyen TTD, et al. Fusobacterium nucleatum induces proliferation and migration in pancreatic cancer cells through host autocrine and paracrine signaling[J]. Sci Signal, 2022, 15(756):eabn4948.
[36]	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.
[37]	Chen Y, Yang S, Tavormina J, et al. Oncogenic collagenⅠhomotrimers from cancer cells bind to α3β1 integrin and impact tumor microbiome and immunity to promote pancreatic cancer[J]. Cancer Cell, 2022, 40(8):818-834, e9.
[38]	Alam A, Levanduski E, Denz P, et al. Fungal mycobiome drives IL-33 secretion and type 2 immunity in pancreatic cancer[J]. Cancer Cell, 2022, 40(2):153-167, e11.
[39]	Vitiello GA, Cohen DJ, Miller G. Harnessing the microbiome for pancreatic cancer immunotherapy[J]. Trends Cancer, 2019, 5(11):670-676.
[40]	Zambirinis CP, Levie E, Nguy S, et al. TLR9 ligation in pancreatic stellate cells promotes tumorigenesis[J]. J Exp Med, 2015, 212(12):2077-2094.
[41]	Okuno K, Tokunaga M, Von Hoff D, et al. Intratumoral malasseziaglobosa levels predict survival and therapeutic response to adjuvant chemotherapy in patients with pancreatic ductal adenocarcinoma[J]. Gastroenterology, 2023, 165(2):502-504, e2.
[42]	Li S, Yang M, Ji L, et al. A multi-omics machine learning framework in predicting the recurrence and metastasis of patients with pancreatic adenocarcinoma[J]. Front Microbiol, 2022, 13: 1032623.
[43]	Chu CS, Yang CY, Yeh CC, et al. Endoscopic ultrasound-guided fine-needle biopsy as a tool for studying the intra-tumoral microbiome in pancreatic ductal adenocarcinoma: a pilot study[J]. Sci Rep, 2022, 12(1):107.
[44]	Gleeson FC, Jeraldo P, Levy MJ, et al. Composition, diversity and potential utility of intervention-naïve pancreatic cancer intratumoral microbiome signature profiling via endoscopic ultrasound[J]. Gut, 2022, 71(2):441-443.
[45]	Chen SM, Chieng WW, Huang SW, et al. The synergistic tumor growth-inhibitory effect of probiotic Lactobacillus on transgenic mouse model of pancreatic cancer treated with gemcitabine[J]. Sci Rep, 2020, 10(1):20319.
[46]	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, e16.
[47]	Lehouritis P, Cummins J, Stanton M, et al. Local bacteria affect the efficacy of chemotherapeutic drugs[J]. Sci Rep, 2015, 5: 14554.
[48]	Xu JW, Wang L, Cheng YG, et al. Immunotherapy for pancreatic cancer: a long and hopeful journey[J]. Cancer Lett, 2018, 425: 143-151.
[49]	Sethi V, Vitiello GA, Saxena D, et al. The role of the microbiome in immunologic development and its implication for pancreatic cancer immunotherapy[J]. Gastroenterology, 2019, 156(7):2097-2115, e2.
[50]	Miyabayashi K, Ijichi H, Fujishiro M. The role of the microbiome in pancreatic cancer[J]. Cancers, 2022, 14(18):4479.
[51]	Sivan A, Corrales L, Hubert N, et al. Commensal Bifidobacterium promotes antitumor immunity and facilitates anti-PD-L1 efficacy[J]. Science, 2015, 350(6264):1084-1089.
[52]	Zhang Z, Tang D. The huge clinical potential of microbiota in the treatment of pancreatic cancer: the next frontier[J]. Biochim Biophys Acta Rev Cancer, 2022, 1877(3):188733.
[53]	Fulop DJ, Zylberberg HM, Wu YL, et al. Association of antibiotic receipt with survival among patients with metastatic pancreatic ductal adenocarcinoma receiving chemotherapy[J]. JAMA Netw Open, 2023, 6(3):e234254.
[54]	Weniger M, Hank T, Qadan M, et al. Influence of Klebsiella pneumoniae and quinolone treatment on prognosis in patients with pancreatic cancer[J]. Br J Surg, 2021, 108(6):709-716.
[55]	Kita A, Fujiya M, Konishi H, et al. Probiotic-derived ferrichrome inhibits the growth of refractory pancreatic cancer cells[J]. Int J Oncol, 2020, 57(3):721-732.
[56]	Kim VM, Blair AB, Lauer P, et al. Anti-pancreatic tumor efficacy of a Listeria-based, Annexin A2-targeting immunotherapy in combination with anti-PD-1 antibodies[J]. J Immunother Cancer, 2019, 7(1):132.
[57]	Murphy C, Rettedal E, Lehouritis P, et al. Intratumoural production of TNFα by bacteria mediates cancer therapy[J]. PLoS One, 2017, 12(6):e0180034.

Please choose a citation manager

Content to export