REFERENCES
1. Wroblewski LE, Peek RM Jr, Wilson KT. Helicobacter pylori and gastric cancer: factors that modulate disease risk. Clin Microbiol Rev. 2010;23:713-39.
2. Salvatori S, Marafini I, Laudisi F, Monteleone G, Stolfi C. Helicobacter pylori and gastric cancer: pathogenetic mechanisms. Int J Mol Sci. 2023;24:2895.
3. Walboomers JMM, Jacobs MV, Manos MM, et al. Human papillomavirus is a necessary cause of invasive cervical cancer worldwide. J Pathol. 1999;189:12-9.
5. Wu S, Rhee KJ, Albesiano E, et al. A human colonic commensal promotes colon tumorigenesis via activation of T helper type 17 T cell responses. Nat Med. 2009;15:1016-22.
6. Kostic AD, Gevers D, Pedamallu CS, et al. Genomic analysis identifies association of Fusobacterium with colorectal carcinoma. Genome Res. 2012;22:292-8.
7. Castellarin M, Warren RL, Freeman JD, et al. Fusobacterium nucleatum infection is prevalent in human colorectal carcinoma. Genome Res. 2012;22:299-306.
8. Geller LT, Barzily-Rokni M, Danino T, et al. Potential role of intratumor bacteria in mediating tumor resistance to the chemotherapeutic drug gemcitabine. Science. 2017;357:1156-60.
9. Nejman D, Livyatan I, Fuks G, et al. The human tumor microbiome is composed of tumor type-specific intracellular bacteria. Science. 2020;368:973-80.
10. Riquelme E, Zhang Y, Zhang L, et al. Tumor microbiome diversity and composition influence pancreatic cancer outcomes. Cell. 2019;178:795-806.e12.
11. Mai Z, Fu L, Su J, To KKW, Yang C, Xia C. Intra-tumoral sphingobacterium multivorum promotes triple-negative breast cancer progression by suppressing tumor immunosurveillance. Mol Cancer. 2025;24:6.
12. von Frieling J, Fink C, Hamm J, et al. Grow with the challenge - microbial effects on epithelial proliferation, carcinogenesis, and cancer therapy. Front Microbiol. 2018;9:2020.
13. Dong X, Yang J, He L, et al. The barrier-microbiota-inflammation axis in colorectal cancer: mechanisms and emerging diagnostic & therapeutic strategies. Cancers (Basel). 2026;18:576.
14. Tingting Y, Xiaoling Z, Yu Z, et al. Interaction of intratumoral microbiota with the tumor immune microenvironment and its impact on cancer progression. Front Oncol. 2025;15:1609889.
15. Quagliariello V, Forte P, Ciappina G, et al. Fusobacteriumnucleatum: pathophysiological and clinical involvement in inflammatory bowel diseases, colorectal cancer and cardiovascular diseases. Cancers (Basel). 2025;17:3348.
16. Liao K, Wen J, Liu Z, et al. The role of intratumoral microbiome in the occurrence, proliferation, metastasis of colorectal cancer and its underlying therapeutic strategies. Ageing Res Rev. 2025;111:102820.
17. Yin Y, Zhang J, Guo Q, Shen C. Research and progress on the association of porphyromonas gingivalis with lung cancer. Zhongguo Fei Ai Za Zhi. 2024;27:799-804.(in Chinese).
18. Liu Y, Yuan X, Chen K, et al. Clinical significance and prognostic value of Porphyromonas gingivalis infection in lung cancer. Transl Oncol. 2021;14:100972.
20. Shi Z, Li Z, Zhang M. Emerging roles of intratumor microbiota in cancer: tumorigenesis and management strategies. J Transl Med. 2024;22:837.
21. Takahashi M, Sukowati EW, Nomura S, et al. Impact of tumoral structure and bacterial species on growth and biodistribution of live bacterial therapeutics in xenografted tumours. J Drug Target. 2023;31:194-205.
22. Luo YC, Huang XT, Wang R, et al. Advancements in understanding tumor-resident bacteria and their application in cancer therapy. Mil Med Res. 2025;12:38.
24. Fu A, Yao B, Dong T, et al. Tumor-resident intracellular microbiota promotes metastatic colonization in breast cancer. Cell. 2022;185:1356-1372.e26.
25. Yan D, Yu Y, Liang C, et al. Intratumoral microbiome: the double-edged sword in remodeling cancer immunotherapy. Mol Cancer. 2026;25:43.
26. Chen F, Guo S, Li Y, et al. Fusobacterium nucleatum-driven CX3CR1+ PD-L1+ phagocytes route to tumor tissues and reshape tumor microenvironment. Gut Microbes. 2025;17:2442037.
27. Schorr L, Mathies M, Elinav E, Puschhof J. Intracellular bacteria in cancer-prospects and debates. NPJ Biofilms Microbiomes. 2023;9:76.
28. Fu A, Yao B, Dong T, Cai S. Intracellular microbes empower cancer metastasis. Life Med. 2022;1:61-3.
29. Bautista J, Fuentes-Yépez MP, Adatty-Molina J, López-Cortés A. Microbial signatures in metastatic cancer. Front Med (Lausanne). 2025;12:1654792.
30. Zhang J, You Z, Li X, Hu J, Li J, Jing Z. Harnessing intratumoral microbiota: new horizons in immune microenvironment and immunotherapy. J Transl Med. 2025;23:897.
31. Shigematsu Y, Saito R, Amori G, et al. Fusobacterium nucleatum, immune responses, and metastatic organ diversity in colorectal cancer liver metastasis. Cancer Sci. 2024;115:3248-55.
32. Parhi L, Alon-Maimon T, Sol A, et al. Breast cancer colonization by Fusobacterium nucleatum accelerates tumor growth and metastatic progression. Nat Commun. 2020;11:3259.
33. McKinley KNL, Herremans KM, Riner AN, et al. Translocation of oral microbiota into the pancreatic ductal adenocarcinoma tumor microenvironment. Microorganisms. 2023;11:1466.
34. Bullman S, Pedamallu CS, Sicinska E, et al. Analysis of Fusobacterium persistence and antibiotic response in colorectal cancer. Science. 2017;358:1443-8.
35. Vayakkattil AB, Pazhanchery AS, Andrews S, Vayakkattil U. The Warburg effect redefined: a kinetic and regulatory perspective. Cureus. 2025;17:e93331.
36. Li J, Zhou Y, Liu Y, et al. Sorafenib inhibits caspase-1 expression through suppressing TLR4/stat3/SUMO1 pathway in hepatocellular carcinoma. Cancer Biol Ther. 2018;19:1057-64.
37. Lan X, Zhang F, Cui G, et al. Microbiota-directed lactic acid depleting nanoenzyme reactivates antitumor immunity and chemosensitivity in hypoxic tumor. Mater Today Bio. 2025;35:102493.
38. Situ Y, Zhang P, Zhang C, et al. The metabolic dialogue between intratumoural microbes and cancer: implications for immunotherapy. EBioMedicine. 2025;115:105708.
39. Cochrane K, Robinson AV, Holt RA, Allen-Vercoe E. A survey of Fusobacterium nucleatum genes modulated by host cell infection. Microb Genom. 2020;6:e000300.
40. Kwon B. A metabolite of the gut microbiota: a facilitator of chemotherapy efficacy in cancer. Signal Transduct Target Ther. 2023;8:238.
41. Kong S, Zhang J, Wang L, et al. Mechanisms of low MHC I expression and strategies for targeting MHC I with small molecules in cancer immunotherapy. Cancer Lett. 2025;611:217432.
42. Lin P, Lin Y, Chen X, Zhao X, Cui L. Decoding MHC loss: molecular mechanisms and implications for immune resistance in cancer. Clin Transl Med. 2025;15:e70403.
43. Wang X, Wang J, Wang Q, Ding G, Huang Y, Feng Y. Precision cytokine modulation to overcome tumor microenvironment-driven resistance to immune checkpoint blockade. Biochim Biophys Acta Rev Cancer. 2026;1881:189536.
44. Li H, Jin W, Liu J, et al. Optimizing mitochondria function in immune cells: implications for cancer immunotherapy. Trends Cancer. 2025;11:1170-84.
45. Kyriazi AA, Karaglani M, Agelaki S, Baritaki S. Intratumoral microbiome: foe or friend in reshaping the tumor microenvironment landscape? Cells. 2024;13:1279.
46. Noor F, Noor H. Metabolic causal factor of immune cell function and fate in the tumor microenvironment. Bull Cancer. 2026;113:777-88.
47. Xu J, Tang Z. Progress on angiogenic and antiangiogenic agents in the tumor microenvironment. Front Oncol. 2024;14:1491099.
48. Wang R, Zhang R, Zhou J, Ran J. Crosstalk between anti-angiogenic and pro-angiogenic pathways in disease: mechanisms and therapeutic strategies. Pharmacol Ther. 2025;276:108934.
49. Peng W, Huang X, Pu Y, et al. The bidirectional regulatory effects of bacteria on blood vessels in the tumor microenvironment. Discov Oncol. 2025;16:2011.
50. Liu C, Fu L, Wang Y, Yang W. Influence of the gut microbiota on immune cell interactions and cancer treatment. J Transl Med. 2024;22:939.
51. Bertocchi A, Carloni S, Ravenda PS, et al. Gut vascular barrier impairment leads to intestinal bacteria dissemination and colorectal cancer metastasis to liver. Cancer Cell. 2021;39:708-724.e11.
52. Gong L, Yang S, Huang J, Li Y. Modulation of gut microbiota in targeted cancer therapy: insights on the EGFR/VEGF/KRAS pathways. Cancer Biol Med. 2024;21:1141-55.
53. Abe S, Masuda A, Matsumoto T, et al. Impact of intratumoral microbiome on tumor immunity and prognosis in human pancreatic ductal adenocarcinoma. J Gastroenterol. 2024;59:250-62.
54. Yuan L, Pan L, Wang Y, et al. Characterization of the landscape of the intratumoral microbiota reveals that Streptococcus anginosus increases the risk of gastric cancer initiation and progression. Cell Discov. 2024;10:117.
55. Fu K, Cheung AHK, Wong CC, et al. Streptococcus anginosus promotes gastric inflammation, atrophy, and tumorigenesis in mice. Cell. 2024;187:882-896.e17.
56. Wang Z, Zhang T, Liu Y. Emerging technologies and current challenges in intratumoral microbiota research. Front Cell Infect Microbiol. 2025;15:1685862.
57. Fu A, Yao B, Dong T, Cai S. Emerging roles of intratumor microbiota in cancer metastasis. Trends Cell Biol. 2023;33:583-93.
58. Harmak Z, Kone AS, Ghouzlani A, Ghazi B, Badou A. Beyond tumor borders: intratumoral microbiome effects on tumor behavior and therapeutic responses. Immune Netw. 2024;24:e40.
59. He X, Mishchuk DO, Shah J, Weimer BC, Slupsky CM. Cross-talk between E. coli strains and a human colorectal adenocarcinoma-derived cell line. Sci Rep. 2013;3:3416.
60. Liu Y, Mei W, Huang X, Yao X, Kong C, Chen Y. Characteristic metabolite profile of 10 colorectal cancer-related bacteria. Front Oncol. 2025;15:1604876.
61. Greathouse KL, Stone JK, Harris CC. Cancer-type-specific bacteria: freeloaders or partners? Cancer Cell. 2020;38:158-60.
62. Khan ZA, Sobkowiak MJ, Ghorbani M, et al. Survival mechanism of pancreatic tumor bacteria and their ability to metabolize chemotherapy drugs. Microbiol Spectr. 2025;13:e0182025.
63. Kwiatkowska AM, Guzmán JA, Lafaurie GI, Castillo DM, Cardona AF. Exploring the role of the oral microbiome in saliva, sputum, bronchoalveolar fluid, and lung cancer tumor tissue: a systematic review. Transl Oncol. 2025;62:102557.
64. Zhao F, An R, Ma Y, et al. Integrated spatial multi-omics profiling of Fusobacterium nucleatum in breast cancer unveils its role in tumour microenvironment modulation and cancer progression. Clin Transl Med. 2025;15:e70273.
65. Li Y, Wang Y, Li X, Liu C. Hunting field: insights on distribution pattern of bacteria and immune cells in solid tumors. Natl Sci Rev. 2021;8:nwab023.
66. Hilmi M, Kamal M, Vacher S, et al. Intratumoral microbiome is driven by metastatic site and associated with immune histopathological parameters: an ancillary study of the SHIVA clinical trial. Eur J Cancer. 2023;183:152-61.
67. Brennan CA, Garrett WS. Fusobacterium nucleatum - symbiont, opportunist and oncobacterium. Nat Rev Microbiol. 2019;17:156-66.
68. Pignatelli P, Nuccio F, Piattelli A, Curia MC. The role of Fusobacterium nucleatum in oral and colorectal carcinogenesis. Microorganisms. 2023;11:2358.
69. Wang P, Huang Q, Zhu Y, Chen L, Ye K. Fusobacterium nucleatum promotes microsatellite instability in colorectal carcinoma through up-regulation of miRNA-155-5p-targeted inhibition of MSH6 via the TLR4/NF-κB signaling pathway. Adv Biol (Weinh). 2024;8:e2400293.
70. Starska-Kowarska K. The role of porphyromonas gingivalis in oral carcinogenesis and progression by remodelling the tumour microenvironment: a narrative review. Cancers (Basel). 2025;17:3478.
71. Zeng R, Sung JJY, Yu J. New pathogen for gastric cancer: streptococcus anginosus. Clin Transl Med. 2024;14:e70104.
72. Kowsarkhizi AS, Yousefi B, Rahimi A, Aliramezani A. Targeting Fusobacterium nucleatum in colorectal cancer: therapeutic strategies and future directions. Infect Agent Cancer. 2025;20:70.
73. Choy ATF, Carnevale I, Coppola S, et al. The microbiome of pancreatic cancer: from molecular diagnostics to new therapeutic approaches to overcome chemoresistance caused by metabolic inactivation of gemcitabine. Expert Rev Mol Diagn. 2018;18:1005-9.
74. Zhang G, Sun D. The synthesis of the novel Escherichia coli toxin-colibactin and its mechanisms of tumorigenesis of colorectal cancer. Front Microbiol. 2024;15:1501973.
75. Taieb F, Petit C, Nougayrède JP, Oswald E. The enterobacterial genotoxins: cytolethal distending toxin and colibactin. EcoSal Plus. 2016:7.
76. Saccheri F, Pozzi C, Avogadri F, et al. Bacteria-induced gap junctions in tumors favor antigen cross-presentation and antitumor immunity. Sci Transl Med. 2010;2:44ra57.
77. Li F, Yang Z, Savage TM, et al. Programmable bacteria synergize with PD-1 blockade to overcome cancer cell-intrinsic immune resistance mechanisms. Sci Immunol. 2024;9:eadn9879.
78. Pushalkar S, Hundeyin M, Daley D, et al. The pancreatic cancer microbiome promotes oncogenesis by induction of innate and adaptive immune suppression. Cancer Discov. 2018;8:403-16.
79. Ochi A, Nguyen AH, Bedrosian AS, et al. MyD88 inhibition amplifies dendritic cell capacity to promote pancreatic carcinogenesis via Th2 cells. J Exp Med. 2012;209:1671-87.
80. Andrade WA, Firon A, Schmidt T, et al. Group B streptococcus degrades cyclic-di-AMP to modulate STING-dependent type I interferon production. Cell Host Microbe. 2016;20:49-59.
81. Yu L, Liu P. Cytosolic DNA sensing by cGAS: regulation, function, and human diseases. Signal Transduct Target Ther. 2021;6:170.
82. Wang L, Jiang W, Yang M, Danzeng Q, Liu S, Cui M. Combination strategies of gut microbiota in cancer therapy through metabolic reprogramming and immune remodeling. Cell Commun Signal. 2025;23:270.
83. Johnson SA, Ormsby MJ, Wessel HM, et al. Monocytes mediate Salmonella Typhimurium-induced tumor growth inhibition in a mouse melanoma model. Eur J Immunol. 2021;51:3228-38.
84. Tsuda K, Yamanaka K, Linan W, et al. Intratumoral injection of Propionibacterium acnes suppresses malignant melanoma by enhancing Th1 immune responses. PLoS One. 2011;6:e29020.
85. Hajjar R, Richard CS, Santos MM. The role of butyrate in surgical and oncological outcomes in colorectal cancer. Am J Physiol Gastrointest Liver Physiol. 2021;320:G601-8.
86. Huang X, Bishehsari F. Microbial imprints on colorectal cancer: the epigenetic silencing of PHLPP1 as a prognostic nexus. BMJ Oncol. 2025;4:e000883.
87. Eaton SE, Kaczmarek J, Mahmood D, et al. Exploiting dietary fibre and the gut microbiota in pelvic radiotherapy patients. Br J Cancer. 2022;127:2087-98.
88. 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. Immunity. 2015;42:344-55.
89. Yu T, Guo F, Yu Y, et al. Fusobacterium nucleatum promotes chemoresistance to colorectal cancer by modulating autophagy. Cell. 2017;170:548-563.e16.
90. Shi Y, Zheng W, Yang K, et al. Intratumoral accumulation of gut microbiota facilitates CD47-based immunotherapy via STING signaling. J Exp Med. 2020:217.
91. Han ZY, Fu ZJ, Wang YZ, et al. Probiotics functionalized with a gallium-polyphenol network modulate the intratumor microbiota and promote anti-tumor immune responses in pancreatic cancer. Nat Commun. 2024;15:7096.
92. Zheng SH, Li KZ, Feng G, et al. Gut microbiota reshaping the pancreatic cancer immune microenvironment: new avenues for immunotherapy. Mol Cancer. 2025;24:313.
93. Yang L, Li A, Wang Y, Zhang Y. Intratumoral microbiota: roles in cancer initiation, development and therapeutic efficacy. Signal Transduct Target Ther. 2023;8:35.
94. Shalapour S, Karin M. Cruel to be kind: epithelial, microbial, and immune cell interactions in gastrointestinal cancers. Annu Rev Immunol. 2020;38:649-71.
95. Silver NL, Dai J, Kerr TD, et al. Intratumoral bacteria are immunosuppressive and promote immunotherapy resistance in head and neck squamous cell carcinoma. Nat Cancer. 2026;7:80-97.
96. Vella G, Rescigno M. Cancer microbiota: a focus on tumor-resident bacteria. EMBO Rep. 2025;26:2977-93.
97. Rubinstein MR, Baik JE, Lagana SM, et al. Fusobacterium nucleatum promotes colorectal cancer by inducing Wnt/β-catenin modulator Annexin A1. EMBO Rep. 2019;20:e47638.
98. Zhou X, Pan X, Shen Z, et al. Eliminating intratumoral bacteria with cGAS-STING-activating nanodrug-bacteria biohybrids potentiates cancer immunotherapy. Biomaterials. 2026;325:123629.
99. Arjunan P, Meghil MM, Pi W, et al. Oral pathobiont activates anti-apoptotic pathway, promoting both immune suppression and oncogenic cell proliferation. Sci Rep. 2018;8:16607.
100. Lin X, Kang K, Chen P, et al. Regulatory mechanisms of PD-1/PD-L1 in cancers. Mol Cancer. 2024;23:108.
101. Chen J, Singh N, Ye X, Theune EV, Wang K. Gut microbiota-mediated activation of GSDMD ignites colorectal tumorigenesis. Cancer Gene Ther. 2024;31:1007-17.
102. Malvankar S, Jaiswal P, Bhat PP, Mehto S. Regulation of cancer by inflammasomes: from inflammation to tumorigenesis. Front Immunol. 2025;16:1611719.
103. Grivennikov SI, Karin M. Dangerous liaisons: STAT3 and NF-kappaB collaboration and crosstalk in cancer. Cytokine Growth Factor Rev. 2010;21:11-9.
104. He G, Karin M. NF-κB and STAT3 - key players in liver inflammation and cancer. Cell Res. 2011;21:159-68.
105. Senthil Kumar S, Gunda V, Reinartz DM, et al. Oral streptococci S. anginosus and S. mitis induce distinct morphological, inflammatory, and metabolic signatures in macrophages. Infect Immun. 2024;92:e0053623.
106. Rubinstein MR, Wang X, Liu W, Hao Y, Cai G, Han YW. Fusobacterium nucleatum promotes colorectal carcinogenesis by modulating E-cadherin/β-catenin signaling via its FadA adhesin. Cell Host Microbe. 2013;14:195-206.
107. 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. Gastroenterology. 2017;152:851-866.e24.
108. Li L, He S, Liao B, et al. Orally administrated hydrogel harnessing intratumoral microbiome and microbiota-related immune responses for potentiated colorectal cancer treatment. Research (Wash D C). 2024;7:0364.
109. Sadeghloo Z, Ebrahimi S, Hakemi-Vala M, Totonchi M, Sadeghi A, Fatemi N. Fusobacterium nucleatum and non-coding RNAs: orchestrating oncogenic pathways in colorectal cancer. Gut Pathog. 2025;17:78.
110. He S, Zheng L, Qi C. Myeloid-derived suppressor cells (MDSCs) in the tumor microenvironment and their targeting in cancer therapy. Mol Cancer. 2025;24:5.
111. Zou Y, Zhang H, Liu F, Chen ZS, Tang H. Intratumoral microbiota in orchestrating cancer immunotherapy response. J Transl Int Med. 2024;12:540-2.
112. Guo J, Zhu P, Li J, et al. Fusobacterium nucleatum promotes PD-L1 expression in cancer cells to evade CD8+ T cell killing in breast cancer. Hum Immunol. 2024;85:111168.
113. Erturk-Hasdemir D, Oh SF, Okan NA, et al. Symbionts exploit complex signaling to educate the immune system. Proc Natl Acad Sci U S A. 2019;116:26157-66.
114. Luu M, Weigand K, Wedi F, et al. Regulation of the effector function of CD8+ T cells by gut microbiota-derived metabolite butyrate. Sci Rep. 2018;8:14430.
115. Lu Q, Wu J, Yu X, Qian J, Song Z. Unveiling the interplay between microbiota and PD1/PD-L1 axis in tumor immunity and immunotherapy. Front Immunol. 2025;16:1690374.
116. Tan Q, Cao X, Zou F, Wang H, Xiong L, Deng S. Spatial heterogeneity of intratumoral microbiota: a new frontier in cancer immunotherapy resistance. Biomedicines. 2025;13:1261.
117. Kalaora S, Nagler A, Nejman D, et al. Identification of bacteria-derived HLA-bound peptides in melanoma. Nature. 2021;592:138-43.
118. Chen J, Deutsch E, Kroemer G, Galluzzi L, Zitvogel L. The microbiota in radiotherapy-induced cancer immunosurveillance. Nat Rev Clin Oncol. 2025;22:667-79.
119. Benej M, Hoyd R, Kreamer M, et al.; exORIEN Consortium. The tumor microbiome reacts to hypoxia and can influence response to radiation treatment in colorectal cancer. Cancer Res Commun. 2024;4:1690-701.
120. Dolmans DE, Fukumura D, Jain RK. Photodynamic therapy for cancer. Nat Rev Cancer. 2003;3:380-7.
121. Kong F, Fang C, Zhang Y, et al. Abundance and metabolism disruptions of intratumoral microbiota by chemical and physical actions unfreeze tumor treatment resistance. Adv Sci (Weinh). 2022;9:e2105523.
122. Diop K, Mbaye B, Nili S, et al. Coupling culturomics and metagenomics sequencing to characterize the gut microbiome of patients with cancer treated with immune checkpoint inhibitors. Gut Pathog. 2025;17:21.
123. He X, Zhao Q, Zhang J, et al. Potential and application of Fusobacterium nucleatum in the diagnosis and treatment of colorectal cancer. Front Microbiol. 2025;16:1652702.
124. Asgharzadeh S, Pourhajibagher M, Bahador A. The microbial landscape of tumors: a deep dive into intratumoral microbiota. Front Microbiol. 2025;16:1542142.
125. Feigenberg SJ, Costabile F, Tanes C, et al. Enhancing outcomes in medically inoperable early-stage NSCLC with gut-targeted antibiotics and stereotactic body radiotherapy: results from a randomized pilot study. J Immunother Cancer. 2025;13:e011356.
126. Singh S, Kim GH, Baek KR, Seo SO. Anti-cancer strategies using anaerobic spore-forming bacteria clostridium: advances and synergistic approaches. Life (Basel). 2025;15:465.
