Advances in Molecular OncologyAdvances in Molecular OncologyУспехи молекулярной онкологии2313-805X2413-3787Publishing House ABV Press72610.17650/2313-805X-2024-11-4-8-22REVIEW ARTICLESОБЗОРНЫЕ СТАТЬИMechanistic and epidemiological evidence on the relationship between microbiota, virome and carcinogenesisМеханистические и эпидемиологические данные о роли микробиоты и вирома в канцерогенезеhttps://orcid.org/0000-0002-9710-8178YakubovskayaM. G.ЯкубовскаяМ. Г.
Russian Federation

Marianna Gennadievna Yakubovskaya

24 Kashirskoe Shosse, Moscow 115522

6 Miklukho-Maklaya St., Moscow 117198

Марианна Геннадиевна Якубовская

115522 Москва, Каширское шоссе, 24

117198 Москва, ул. Миклухо-Маклая, 6

mgyakubovskaya@mail.ruhttps://orcid.org/0000-0002-5082-9883FetisovT. I.ФетисовТ. И.
Russian Federation

24 Kashirskoe Shosse, Moscow 115522

6 Miklukho-Maklaya St., Moscow 117198

115522 Москва, Каширское шоссе, 24

117198 Москва, ул. Миклухо-Маклая, 6

https://orcid.org/0000-0002-4443-8376SolenovaL. G.СоленоваЛ. Г.
Russian Federation

24 Kashirskoe Shosse, Moscow 115522

115522 Москва, Каширское шоссе, 24

https://orcid.org/0000-0002-4224-6303RyzhovaN. I.РыжоваН. И.
Russian Federation

24 Kashirskoe Shosse, Moscow 115522

115522 Москва, Каширское шоссе, 24

https://orcid.org/0000-0001-8077-2307LokhoninaA. V.ЛохонинаА. В.
Russian Federation

6 Miklukho-Maklaya St., Moscow 117198

117198 Москва, ул. Миклухо-Маклая, 6

https://orcid.org/0009-0004-3482-8954AntonovaI. A.АнтоноваИ. А.
Russian Federation

24 Kashirskoe Shosse, Moscow 115522

115522 Москва, Каширское шоссе, 24

https://orcid.org/0000-0002-3167-7204BelitskyG. A.БелицкийГ. А.
Russian Federation

24 Kashirskoe Shosse, Moscow 115522

115522 Москва, Каширское шоссе, 24

https://orcid.org/0000-0002-8599-6833KirsanovK. I.КирсановК. И.
Russian Federation

24 Kashirskoe Shosse, Moscow 115522

6 Miklukho-Maklaya St., Moscow 117198

115522 Москва, Каширское шоссе, 24

117198 Москва, ул. Миклухо-Маклая, 6

https://orcid.org/0000-0003-1787-2676AginovaV. V.АгиноваВ. В.
Russian Federation

Viktoriya Viktorovna Aginova

24 Kashirskoe Shosse, Moscow 115522

Виктория Викторовна Агинова

115522 Москва, Каширское шоссе, 24

v.aginova@ronc.ruN.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of RussiaФГБУ «Национальный медицинский исследовательский центр онкологии им. Н.Н. Блохина» Минздрава РоссииPeoples’ Friendship University of RussiaФГАОУ ВО «Российский университет дружбы народов»151220241148220912202409122024Copyright ©; 2024, Yakubovskaya M.G., Fetisov T.I., Solenova L.G., Ryzhova N.I., Lokhonina A.V., Antonova I.A., Belitsky G.A., Kirsanov K.I., Aginova V.V.Copyright ©; 2024, Якубовская М.Г., Фетисов Т.И., Соленова Л.Г., Рыжова Н.И., Лохонина А.В., Антонова И.А., Белицкий Г.А., Кирсанов К.И., Агинова В.В.2024Yakubovskaya M.G., Fetisov T.I., Solenova L.G., Ryzhova N.I., Lokhonina A.V., Antonova I.A., Belitsky G.A., Kirsanov K.I., Aginova V.V.Якубовская М.Г., Фетисов Т.И., Соленова Л.Г., Рыжова Н.И., Лохонина А.В., Антонова И.А., Белицкий Г.А., Кирсанов К.И., Агинова В.В.https://creativecommons.org/licenses/by/4.0https://umo.abvpress.ru/jour/article/view/726

Recent development of molecular and genetic technologies has demonstrated at the molecular level the co-evolutionary principles of interaction between microbiota, virome and the host organism, as well as the role of microorganisms and viruses both in maintaining physiological homeostasis and in the development of various diseases, including malignant neoplasms. The presented review is devoted to the analysis and generalization of modern data on microorganisms and viruses inhabiting the human body, their role in the processes of initiation, promotion and progression of carcinogenesis. The review provides information on known oncogenic viruses and microorganisms according to the modern classification of carcinogenic agents of the International Agency for Research on Cancer. Mechanistic data on the procarcinogenic effect of microbiota and virome are considered in accordance with the modern concept of key characteristics of a carcinogenic agent. Particular attention is paid to the analysis of data on the influence of microbiota and virome on the immunity of the host organism, including both the first results of immunotherapy with Coley toxin of soft tissue sarcomas and osteosarcomas, and data on the influence of individual types of microorganisms on the formation of the immunocompetent cell profile of the host organism. In addition, the influence of intratumor and intracellular microbiota, respectively, on the microenvironment of tumor cells and cellular signaling, including in solid tumors that have no contact with the external environment are also discussed. The data presented are important in terms of the holobiota concept, showing the interdependent existence of the human body, microorganisms and viruses, to improve the prevention and therapy of malignant neoplasms.

Развитие молекулярных и генетических технологий позволило на молекулярном уровне продемонстрировать коэволюционные принципы взаимодействия микробиоты, вирома и организма-хозяина, а также роль микроорганизмов и вирусов в поддержании физиологического гомеостаза и развитии различных заболеваний, включая злокачественные новообразования. представленный обзор посвящен анализу и обобщению современных данных о микроорганизмах и вирусах, населяющих человеческий организм, а также их роли в процессах инициации, промоции и прогрессии канцерогенеза. В статье приведена информация об известных онкогенных вирусах и микроорганизмах с учетом современной классификации канцерогенных агентов международного агентства по изучению рака (International Agency for Research on Cancer). Рассмотрены механистические данные о проканцерогенном воздействии микробиоты и вирома в соответствии с современной концепцией ключевых характеристик канцерогенного агента. Особое внимание уделено анализу данных о влиянии микробиоты и вирома на иммунитет организма-хозяина, включая первые результаты иммунотерапии токсином коли сарком мягких тканей и остеосарком, а также о воздействии отдельных видов микроорганизмов на формирование профиля зрелых иммунокомпетентных клеток организма-хозяина. кроме того, представлены сведения о влиянии внутриопухолевой и внутриклеточной микробиоты на микроокружение опухолевых клеток и клеточный сигналинг, в том числе в солидных опухолях, не имеющих контакта с внешней средой. приведенные данные важны в плане использования концепции холобиота, т. е. взаимозависимого существования организма человека, микроорганизмов и вирусов, для совершенствования профилактики и терапии злокачественных новообразований.

microbiotaviromedysbiosismalignant neoplasmcarcinogenic hazardkey characteristic of a carcinogenic agentantitumor immunitytumor microenvironmentмикробиотавирусдисбиоззлокачественное новообразованиеканцерогенная опасностьключевая характеристика канцерогенного агентапротивоопухолевый иммунитетмикроокружение опухолиThe work was carried out with the financial support of the Russian Science Foundation (grant No. 23-65-00003).Работа выполнена при финансовой поддержке Российского научного фонда (грант № 23-65-00003).Berg G., Rybakova D., Fischer D. et al. Microbiome definition re-visited: old concepts and new challenges. Microbiome 2020;30(8):103. DOI: 10.1186/s40168-020-00875-0Bassler B.L. Small talk: cell-to-cell communication in bacteria. Cell 2002;109(4):421–4. DOI: 10.1016/S0092-8674(02)00749-3Medzhitov R., Preston-Hurlburt P., Janeway C.A. Jr. A human homologue of the Drosophila Toll protein signals activation of adaptive immunity. Nature 1997;388(6640):394–7. DOI: 10.1038/41131Thaiss C.A., Zmora N., Levy M., Elinav E. The microbiome and innate immunity. Nature 2016;535(7610):65–74. DOI: 10.1038/nature18847Silverstein A.M. Paul Ehrlich’s passion: the origins of his receptor immunology. Cell Immunol 1999;194(2):213–21. DOI: 10.1006/cimm.1999.1505Amarante-Mendes G.P., Adjemian S., Branco L.M. et al. Pattern recognition receptors and the host cell death molecular machinery. Front Immunol 2018;9:2379. DOI: 10.3389/fimmu.2018.02379Sender R., Fuchs S., Milo R. Revised estimates for the number of human and bacteria cells in the body. PLoS Biol 2016;14(8):e1002533. DOI: 10.1371/journal.pbio.1002533Sepich-Poore G.D., Zitvogel L., Straussman R. et al. The icrobiome and human cancer. Science 2021;371(6536):eabc4552. DOI: 10.1126/science.abc4552Liang G., Bushman F.D. The human virome: assembly composition and host interactions. Nat Rev Microbiol 2021;19(8):514–27. DOI: 10.1038/s41579-021-00536-5Belyavskaya V.A., Cherdyntseva N.V., Kzhyshkovska J.G., Litvyakov N.V. Microbiome, immune system and cancer: three sides of the one medal. Sibirskiy onkologicheskiy zhurnal = Siberian Journal of Oncology 2022;21(6):131–44. (In Russ.). DOI: 10.21294/1814-4861-2022-21-6-131-144Белявская В.А., Чердынцева Н.В., Кжышковска Ю.Г., Литвяков Н.В. Микробиом, иммунная система и рак: три стороны одной медали. Сибирский онкологический журнал 2022;21(6):131–44. DOI: 10.21294/1814-4861-2022-21-6-131-144Kaybysheva V.O., Zharova M.E., Filimendikova K.Yu. et al. Human microbiome: age-related changes and functions. Dokazatel’naya gastroenterologiya = Russian Journal of Evidence-based Gastroenterology 2020;9(2):42–55. (In Russ.). DOI: 10.17116/dokgastro2020902142Кайбышева В.О., Жарова М.Е., Филимендикова К.Ю., Никонов Е.Л. Микробиом человека: возрастные изменения и функции. Доказательная гастроэнтерология 2020;9(2):42–55. DOI: 10.17116/dokgastro2020902142Mima K., Ogino S., Nakagawa S. et al. The role of intestinal bacteria in the development and progression of gastrointestinal tract neoplasms. Surg Oncol 2017;26(4):368. DOI: 10.1016/j.suronc.2017.07.011Chen J., Domingue J.C., Sears C.L. Microbiota dysbiosis in select human cancers: evidence of association and causality. Semin Immunol 2017;32:25–34. DOI: 10.1016/j.smim.2017.08.001Zitvogel L., Pietrocola F., Kroemer G. Nutrition, inflammation and cancer. Nat Immunol 2017;18(8):843–50. DOI: 10.1038/ni.3754Nejman D., Livyatan I., Fuks G. et al. The human tumor microbiome is composed of tumor type-specific intracellular bacteria. Science 2020;368(6494):973–80. DOI: 10.1126/science.aay9189Samet J.M., Chiu W.A., Cogliano V. et al. The IARC monographs: updated procedures for modern and transparent evidence synthesis in cancer hazard identification. J Natl Cancer Inst 2019;112(1):30–7. DOI: 10.1093/jnci/djz169De Martel C., Georges D., Bray F. et al. Global burden of cancer attributable to infections in 2018: a worldwide incidence analysis. Lancet Glob Health 2020;8(2):e180–90. DOI: 10.1016/S2214-109X(19)30488-7Biological agents. IARC Monographs on the evaluation of carcinogenic risks to humans. IARC, 2012. Vol. 100B. Available at: https://publications.iarc.fr/Book-And-Report-Series/Iarc-Monographs-On-The-Identification-Of-Carcinogenic-Hazards-To-Humans/Biological-Agents-2012.Malaria and some polyomaviruses (SV40, BK, JC, and Markel cell viruses). IARC monographs on the working group on the evaluation of carcinogenic risks to humans. IARC, 2012. Vol. 104. Available at: https://publications.iarc.fr/Book-And-Report-Series/Iarc-Monographs-On-The-Identification-Of-Carcinogenic-Hazards-To-Humans/Malaria-And-Some-Polyomaviruses-SV40-BK-JC-And-Merkel-Cell-Viruses-2013.Shannon-Lowe C., Rickinson A. The global landscape of EBV-associated tumors. Front Oncol 2019;9:713. DOI: 10.3389/fonc.2019.00713Wang Y., Yuan Y., Gu D. Hepatitis B and C virus Infections and the risk of biliary tract cancers: a meta-analysis of observational studies. Infect Agent Cancer 2022;17(1):45. DOI: 10.1186/s13027-022-00457-9Zhang W., Du F., Wang L. et al. Hepatitis virus-associated non-hodgkin lymphoma: pathogenesis and treatment strategies. J Clin Transl Hepatol 2023;11(5):1256–66. DOI: 10.14218/JCTH.2022.00079SLabo N., Whitby D. Kaposi’s sarcoma-associated herpesvirus: epidemiology and clinical features of related cancer. In: Viruses and human cancer. Ed. by S.D. Hudnall. NY: Springer, 2014. Pp. 323–340.Silverberg M.J., Lau B., Achenbach C.J. et al. Cumulative incidence of cancer among HIV-infected individuals in North America. Ann Intern Med 2015;163(7):507–18. DOI: 10.7326/M14-2768Taberna M., Mena M., Pavón M.A. et al. Human papillomavirus-related oropharyngeal cancer. Ann Oncol 2017;28(10):2386–98. DOI: 10.1093/annonc/mdx304Van Dyne E.A., Henley S.J., Saraiya M. et al. Trends in human papillomavirus-associated cancers – United States, 1999–2015. MMWR Morb Mortal Wkly Rep 2018;67(33):918–24. DOI: 10.15585/mmwr.mm6733a2Whiteman D.C., Parma P., Fahey P. et al. Association of Helicobacter Pylori infection with reduced risk for esophageal cancer is independent of environmental and genetic modifiers. Gastroenterology 2010;139(1):73–83. DOI: 10.1053/j.gastro.2010.04.009Wyss K., Granath F., Wångdahl A. et al. Malaria and risk of lymphoid neoplasms and other cancer: a nationwide population-based cohort study. BMC Med 2020;18:296. DOI: 10.1186/s12916-020-01759-8Tan L.S.Y., Fredrik P., Ker L. et al. High-risk HPV genotypes and P16INK4a expression in a cohort of head and neck squamous cell carcinoma patients in singapore. Oncotarget 2016;7(52):86730–9. DOI: 10.18632/oncotarget.13502Dimitraki M.G., Sourvinos G. Merkel cell polyomavirus (MCPyV) and cancers: emergency bell or false alarm? Cancers (Basel) 2022,14(22):5548. DOI: 10.3390/cancers14225548Ceccarelli G., Giovanetti M., Sagnelli C. et al. Human immunodeficiency virus type 2: the neglected threat. Pathogens 2021;10(11):1377. DOI: 10.3390/pathogens10111377Si-Mohamed A., Badoual C., Hans S. et al. An unusual human papillomavirus type 82 detection in laryngeal squamous cell carcinoma: case report and review of literature. J Clin Virol 2012;54(2):190–3. DOI: 10.1016/j.jcv.2012.02.024Wallace J., Gonzalez H., Rajan R. et al. Anti-HIV drugs cause mitochondrial dysfunction in monocyte-derived macrophages. Antimicrob Agents Chemother 2022;66(4):e0194121. DOI: 10.1128/aac.01941-21Passerini S., Prezioso C., Prota A. et al. Detection of human neurotropic JCPyV DNA sequence in pediatric anaplastic xanthoastrocytoma. J Neurovirol 2023;29(2):232–6. DOI: 10.1007/s13365-023-01129-zTavassoli N., Vojdani A., Salimi-Namin S. et al. Human BKV large T genome detection in prostate cancer and benign prostatic hyperplasia tissue samples by nested PCR: a case-control study. Mol Biol Res Commun 2023;12(4):149–54. DOI: 10.22099/mbrc.2023.47537.1836Starrett G.J., Buck C.B. BK Polyomavirus is a cause of bladder cancer. Curr Opin Virol 2019;39:8–15. DOI: 10.1016/j.coviro.2019.06.009Wong Y., Meehan M.T., Burrows S.R. et al. Estimating the global burden of Epstein–Barr virus-related cancers. J Cancer Res Clin Oncol 2022;148(1):31–46. DOI: 10.1007/s00432-021-03824-yIbrahim Khalil A., Franceschi S., de Martel C. et al. Burden of Kaposi sarcoma according to HIV status: a systematic review and global analysis. Int J Cancer 2022;150(12):1948–57. DOI: 10.1002/ijc.33951Hernández-Ramírez R.U., Shiels M.S., Dubrow R., Engels E.A. Cancer risk in HIV-infected people in the USA from 1996 to 2012: a population-based, registry-linkage study. Lancet HIV 2017;4(11):e495–504. DOI: 10.1016/S2352-3018(17)30125-XHuman immunodeficiency viruses and human T-cell lymphotropic viruses. IARC monographs on the evaluation of carcinogenic risks to humans. IARC, 2012. Vol. 67. Available at: https://publications.iarc.fr/Book-And-Report-Series/Iarc-Monographs-On-The-Identification-Of-Carcinogenic-Hazards-To-Humans/Human-Immunodeficiency-Viruses-And-Human-T-Cell-Lymphotropic-Viruses-1996.Mirzaei R., Afaghi A., Babakhani S. et al. Role of microbiota-derived short-chain fatty acids in cancer development and prevention. Biomed Pharmacother 2021;139:111619. DOI: 10.1016/j.biopha.2021.111619Nougayrède J.-P., Homburg S., Taieb F. et al. Escherichia Coli induces DNA double-strand breaks in eukaryotic cells. Science 2006:313(5788):848–51. DOI: 10.1126/science.1127059Hartl K., Sigal M. Microbe-driven genotoxicity in gastrointestinal carcinogenesis. Int J Mol Sci 2020;21(20):7439. DOI: 10.3390/ijms21207439Jones R.M., Mercante J.W., Neish A.S. Reactive oxygen production induced by the gut microbiota: pharmacotherapeutic implications. Curr Med Chem 2012;19(10):1519–29. DOI: 10.2174/092986712799828283Tian X., Liu Z., Niu B. et al. E-cadherin/β-catenin complex and the epithelial barrier. J Biomed Biotechnol 2011;2011:567305. DOI: 10.1155/2011/567305Stein R.A., Riber L. Epigenetic effects of short-chain fatty acids from the large intestine on host cells. Microlife 2023;4. DOI: 10.1093/femsml/uqad032Dzutsev A., Badger J.H., Perez-Chanona E. et al. Microbes and cancer. Annu Rev Immunol 2017;35(1):199–228. DOI: 10.1146/annurev-immunol-051116-052133Turner L., Bitto N.J., Steer D.L. et al. Helicobacter pylori outer membrane vesicle size determines their mechanisms of host cell entry and protein content. Front Immunol 2018;9:1466. DOI: 10.3389/fimmu.2018.01466Shi Y., Meng L., Zhang C. Extracellular vesicles of Lacticaseibacillus paracasei PC-H1 induce colorectal cancer cells apoptosis via PDK1/AKT/Bcl-2 signaling pathway. Microbiol Res 2021;255:126921. DOI: 10.1016/j.micres.2021.126921Pistello M., Antonelli G. Integration of the viral genome into the host cell genome: a double-edged sword. Clin Microbiol Infect 2016;22(4):296–8. DOI: 10.1016/j.cmi.2016.01.022Spurgeon M.E., Liem A., Buehler D. et al. The Merkel cell polyomavirus T antigens function as tumor promoters in murine skin. Cancers (Basel) 2021;13(2):222. DOI: 10.3390/cancers13020222Read S.A., Douglas M.W. Virus induced inflammation and cancer development. Cancer Lett 2014;345(2):174–81. DOI: 10.1016/j.canlet.2013.07.030Nauts H.C., McLaren J.R. Coley toxins – the first century. Adv Exp Med Biol 1990;267:483–500. DOI: 10.1007/978-1-4684-5766-7_52Aghamajidi A., Maleki Vareki S. The effect of the gut microbiota on systemic and anti-tumor immunity and response to systemic therapy against cancer. Cancers (Basel) 2022;14(15):3563. DOI: 10.3390/cancers14153563Wang M., Yang G., Tian Y. et al. The role of the gut microbiota in gastric cancer: the immunoregulation and immunotherapy. Front Immunol 2023;14:1183331. DOI: 10.3389/fimmu.2023.1183331Ivanov I.I. Microbe hunting hits home. Cell Host Microbe 2017;21(3):282–5. DOI: 10.1016/j.chom.2017.02.010Jacouton E., Chain F., Sokol H. et al. Probiotic strain Lactobacillus casei BL23 prevents colitis-associated colorectal cancer. Front Immunol 2017;8:1553. DOI: 10.3389/fimmu.2017.01553Tarrah A., de Castilhos J., Rossi R.C. et al. In vitro probiotic potential and anti-cancer activity of newly isolated folate-producing Streptococcus thermophilus strains. Front Microbiol 2018;9:2214. DOI: 10.3389/fmicb.2018.02214Buret A.G., Motta J.P., Allain T. et al. Pathobiont release from dysbiotic gut microbiota biofilms in intestinal inflammatory diseases: a role for iron? J Biomed Sci 2019;26(1):1. DOI: 10.1186/s12929-018-0495-4Bordon Y. Microbiota: a viral understudy for commensal bacteria. Nat Rev Immunol 2015;15(1):4. DOI: 10.1038/nri3788Kernbauer E., Ding Y., Cadwell K. An enteric virus can replace the beneficial function of commensal bacteria. Nature 2014;516(7529):94–8. DOI: 10.1038/nature13960Champagne-Jorgensen K., Luong T., Darby T., Roach D.R. Immunogenicity of bacteriophages. Trends Microbiol 2023;31(10):1058–71. DOI: 10.1016/j.tim.2023.04.008O’Neill L.A., Golenbock D., Bowie A.G. The history of Toll-like receptors – redefining innate immunity. Nat Rev Immunol 2013;13(6):453–60. DOI: 10.1038/nri3446Jiang T., Zhou C., Ren S. Role of IL-2 in cancer immunotherapy. Oncoimmunology 2016;5(6):e1163462. DOI: 10.1080/2162402X.2016.1163462Considine B., Hurwitz M.E. Current status and future directions of immunotherapy in renal cell carcinoma. Curr Oncol Rep 2019;21(4):34. DOI: 10.1007/s11912-019-0779-1Rosenberg S.A., Yang J.C., Topalian S.L. et al. Treatment of 283 consecutive patients with metastatic melanoma or renal cell cancer using high-dose bolus interleukin 2. JAMA 1994;30;271(12):907–13.Smith M., García-Martínez E., Pitter M.R. et al. Trial watch: Toll-like receptor agonists in cancer immunotherapy. Oncoimmunology 2018;7(12):e1526250. DOI: 10.1080/2162402X.2018.1526250Wu Z., Zhang S., Li L. et al. The gut microbiota modulates responses to anti-PD-1 and chemotherapy combination therapy and related adverse events in patients with advanced solid tumors. Front Oncol 2022;12:887383. DOI: 10.3389/fonc.2022.887383Che S., Yan Z., Feng Y., Zhao H. Unveiling the intratumoral microbiota within cancer landscapes. iScience 2024;27(6):109893. DOI: 10.1016/j.isci.2024.109893Zhang L., Yu L. The role of the microscopic world: exploring the role and potential of intratumoral microbiota in cancer immunotherapy. Medicine (Baltimore) 2024;103(20):e38078. DOI: 10.1097/MD.0000000000038078Perry L.M., Cruz S.M., Kleber K.T. et al. Human soft tissue sarcomas harbor an intratumoral viral microbiome which is linked with natural killer cell infiltrate and prognosis. J Immunother Cancer 2023;11(1):e004285. DOI: 10.1136/jitc-2021-004285Yang L., Li A., Wang Y., Zhang Y. Intratumoral microbiota: roles in cancer initiation, development and therapeutic efficacy. Signal Transduct Target Ther 2023;8(1):35. DOI: 10.1038/s41392-022-01304-4Wu J., Zhang P., Mei W., Zeng C. Intratumoral microbiota: implications for cancer onset, progression, and therapy. Front Immunol 2024;14:1301506. DOI: 10.3389/fimmu.2023.1301506Xu J., Cheng M., Liu J. et al. Research progress on the impact of intratumoral microbiota on the immune microenvironment of malignant tumors and its role in immunotherapy. Front Immunol 2024;15:1389446. DOI: 10.3389/fimmu.2024.1389446Rajasekaran K., Carey R.M., Lin X. et al. The microbiome of HPV-positive tonsil squamous cell carcinoma and neck metastasis. Oral Oncol 2021;117:105305. DOI: 10.1016/j.oraloncology.2021.105305Chiba A., Bawaneh A., Velazquez C. et al. Neoadjuvant chemotherapy shifts breast tumor microbiota populations to regulate drug responsiveness and the development of metastasis. Mol Cancer Res 2020;18(1):130–9. DOI: 10.1158/1541-7786.MCR-19-0451Chen G., Gao C., Jiang S. et al. Fusobacterium nucleatum outer membrane vesicles activate autophagy to promote oral cancer metastasis. J Adv Res 2024;56:167–79. DOI: 10.1016/j.jare.2023.04.002Li L., Chandra V., McAllister F. Tumor-resident microbes: the new kids on the microenvironment block. Trends Cancer 2024;10(4):347–55. DOI: 10.1016/j.trecan.2023.12.002Tiraboschi L., Braga D., Melacarne A. et al. Unveiling the impact of intratumoral microbiota in the treatment efficacy of soft tissue sarcoma. Cancer Res 2024;84(6):1277. DOI: 10.1158/1538-7445.AM2024-1277Camacho E.M., Mesa-Pereira B., Medina C. et al. Engineering Salmonella as intracellular factory for effective killing of tumour cells. Sci Rep 2016:28(6):30591. DOI: 10.1038/srep30591Groot A.J., Mengesha A., van der Wall E. et al. Functional antibodies produced by oncolytic clostridia. Biochem Biophys Res Commun 2007;364(4):985–9. DOI: 10.1016/j.bbrc.2007.10.126Ribas A., Dummer R., Puzanov I. et al. Oncolytic virotherapy promotes intratumoral T cell infiltration and Improves anti-PD-1 immunotherapy. Cell 2017;170(6):1109–19.e10. DOI: 10.1016/j.cell.2017.08.027