{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T20:56:10Z","timestamp":1792097770355,"version":"4.4.0"},"reference-count":106,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2023,11,14]],"date-time":"2023-11-14T00:00:00Z","timestamp":1699920000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Oral mucositis (OM) is a significant complication of cancer therapy with limited management strategies. Whilst inflammation is a central feature of destructive and ultimately ulcerative pathology, to date, attempts to mitigate damage via this mechanism have proven limited. A relatively underexamined aspect of OM development is the contribution of elements of the innate immune system. In particular, the role played by barriers, pattern recognition systems, and microbial composition in early damage signaling requires further investigation. As such, this review highlights the innate immune response as a potential focus for research to better understand OM pathogenesis and development of interventions for patients treated with radiotherapy and chemotherapy. Future areas of evaluation include manipulation of microbial\u2013mucosal interactions to alter cytotoxic sensitivity, use of germ-free models, and translation of innate immune-targeted agents interrogated for mucosal injury in other regions of the alimentary canal into OM-based clinical trials.<\/jats:p>","DOI":"10.3390\/ijms242216314","type":"journal-article","created":{"date-parts":[[2023,11,14]],"date-time":"2023-11-14T09:12:39Z","timestamp":1699953159000},"page":"16314","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["The Role of the Innate Immune Response in Oral Mucositis Pathogenesis"],"prefix":"10.3390","volume":"24","author":[{"given":"Joanne","family":"Bowen","sequence":"first","affiliation":[{"name":"School of Biomedicine, University of Adelaide, Adelaide 5005, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9549-5346","authenticated-orcid":false,"given":"Courtney","family":"Cross","sequence":"additional","affiliation":[{"name":"School of Biomedicine, University of Adelaide, Adelaide 5005, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,11,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1007\/s00280-007-0570-0","article-title":"Characterisation of mucosal changes in the alimentary tract following administration of irinotecan: Implications for the pathobiology of mucositis","volume":"62","author":"Logan","year":"2008","journal-title":"Cancer Chemother. Pharmacol."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Jiang, R., Liu, Y., Zhang, H., Chen, Y., Liu, T., Zeng, J., Nie, E., Chen, S., and Tan, J. (2022). Distinctive microbiota of delayed healing of oral mucositis after radiotherapy of nasopharyngeal carcinoma. Front. Cell. Infect. Microbiol., 12.","DOI":"10.3389\/fcimb.2022.1070322"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1038\/nrc1318","article-title":"The pathobiology of mucositis","volume":"4","author":"Sonis","year":"2004","journal-title":"Nat. Rev. Cancer"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2683","DOI":"10.1007\/s00520-019-05084-6","article-title":"Oral microbial influences on oral mucositis during radiotherapy treatment of head and neck cancer","volume":"28","author":"Vesty","year":"2020","journal-title":"Support. Care Cancer"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1111\/odi.12167","article-title":"Oral mucosal injury in oncology patients: Perspectives on maturation of a field","volume":"21","author":"Peterson","year":"2015","journal-title":"Oral Dis."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1995","DOI":"10.1002\/cncr.20162","article-title":"Perspectives on cancer therapy-induced mucosal injury: Pathogenesis, measurement, epidemiology, and consequences for patients","volume":"100","author":"Sonis","year":"2004","journal-title":"Cancer"},{"key":"ref_7","unstructured":"Peterson, D.E., Keefe, D.M., and Sonis, S.T. (2012). American Society of Clinical Oncology Educational Book, American Society of Clinical Oncology."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"917860","DOI":"10.3389\/froh.2022.917860","article-title":"Precision medicine for risk prediction of oral complications of cancer therapy-The example of oral mucositis in patients receiving radiation therapy for cancers of the head and neck","volume":"3","author":"Sonis","year":"2022","journal-title":"Front. Oral Health"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"4939","DOI":"10.1007\/s00520-021-06108-w","article-title":"A hypothesis for the pathogenesis of radiation-induced oral mucositis: When biological challenges exceed physiologic protective mechanisms. Implications for pharmacological prevention and treatment","volume":"29","author":"Sonis","year":"2021","journal-title":"Support. Care Cancer"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1186\/s13046-020-01715-7","article-title":"Oral mucositis: The hidden side of cancer therapy","volume":"39","author":"Pulito","year":"2020","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1097\/SPC.0000000000000310","article-title":"Advances in the understanding and management of mucositis during stem cell transplantation","volume":"11","author":"Bowen","year":"2017","journal-title":"Curr. Opin. Support. Palliat. Care"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"2823","DOI":"10.2217\/fon-2017-0418","article-title":"US oncology-wide incidence, duration, costs and deaths from chemoradiation mucositis and antimucositis therapy benefits","volume":"13","author":"McCullough","year":"2017","journal-title":"Future Oncol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"lgz010","DOI":"10.1093\/jncimonographs\/lgz010","article-title":"Costs of Oral Complications of Cancer Therapies: Estimates and a Blueprint for Future Study","volume":"2019","author":"Elting","year":"2019","journal-title":"J. Natl. Cancer Inst. Monogr."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1097\/CCO.0000000000000180","article-title":"Mucositis: Pathobiology and management","volume":"27","author":"Villa","year":"2015","journal-title":"Curr. Opin. Oncol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1007\/s40257-018-0384-3","article-title":"Toxic Side Effects of Targeted Therapies and Immunotherapies Affecting the Skin, Oral Mucosa, Hair, and Nails","volume":"19","author":"Lacouture","year":"2018","journal-title":"Am. J. Clin. Dermatol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1230","DOI":"10.1158\/2326-6066.CIR-20-0372","article-title":"Understanding and Overcoming the Inflammatory Toxicities of Immunotherapy","volume":"8","author":"Dougan","year":"2020","journal-title":"Cancer Immunol. Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"4423","DOI":"10.1002\/cncr.33100","article-title":"MASCC\/ISOO clinical practice guidelines for the management of mucositis secondary to cancer therapy","volume":"126","author":"Elad","year":"2020","journal-title":"Cancer"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"7292","DOI":"10.1002\/nop2.1982","article-title":"Nurses\u2019 Knowledge on Assessment and Management of Cancer Therapy-Associated Oral Mucositis","volume":"10","author":"Raymond","year":"2023","journal-title":"Nurs. Open"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1016\/j.critrevonc.2015.11.010","article-title":"Pain management in head and neck cancer patients undergoing chemo-radiotherapy: Clinical practical recommendations","volume":"99","author":"Mirabile","year":"2016","journal-title":"Crit. Rev. Oncol. Hematol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"3949","DOI":"10.1007\/s00520-019-04848-4","article-title":"Systematic review of basic oral care for the management of oral mucositis in cancer patients and clinical practice guidelines","volume":"27","author":"Hong","year":"2019","journal-title":"Support. Care Cancer"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1021","DOI":"10.2147\/DDDT.S267400","article-title":"Superoxide Dismutase as an Intervention for Radiation Therapy-Associated Toxicities: Review and Profile of Avasopasem Manganese as a Treatment Option for Radiation-Induced Mucositis","volume":"15","author":"Sonis","year":"2021","journal-title":"Drug Des. Dev. Ther."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"3985","DOI":"10.1007\/s00520-019-04888-w","article-title":"Systematic review of anti-inflammatory agents for the management of oral mucositis in cancer patients and clinical practice guidelines","volume":"27","author":"Ariyawardana","year":"2019","journal-title":"Support. Care Cancer"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Senel, S. (2021). An Overview of Physical, Microbiological and Immune Barriers of Oral Mucosa. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22157821"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1007\/s00281-018-0701-1","article-title":"The first line of defence: Insights into mechanisms and relevance of phagocytosis in epithelial cells","volume":"40","author":"Gunther","year":"2018","journal-title":"Semin. Immunopathol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"122","DOI":"10.4103\/jomfp.JOMFP_304_18","article-title":"Oral microbiome: Unveiling the fundamentals","volume":"23","author":"Deo","year":"2019","journal-title":"J. Oral Maxillofac. Pathol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"5721","DOI":"10.1128\/JCM.43.11.5721-5732.2005","article-title":"Defining the normal bacterial flora of the oral cavity","volume":"43","author":"Aas","year":"2005","journal-title":"J. Clin. Microbiol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/j.coi.2013.10.016","article-title":"The interplay between the innate immune system and the microbiota","volume":"26","author":"Thaiss","year":"2014","journal-title":"Curr. Opin. Immunol."},{"key":"ref_28","first-page":"317","article-title":"Cell junctions and oral health","volume":"18","author":"Samiei","year":"2019","journal-title":"EXCLI J."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1779","DOI":"10.1007\/s00520-015-2964-6","article-title":"Tight junction defects are seen in the buccal mucosa of patients receiving standard dose chemotherapy for cancer","volume":"24","author":"Wardill","year":"2016","journal-title":"Support. Care Cancer"},{"key":"ref_30","first-page":"3","article-title":"Pathobiology of oral mucositis: Novel insights and opportunities","volume":"5","author":"Sonis","year":"2007","journal-title":"J. Support Oncol."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"M\u00fcller, V.J., Belibasakis, G.N., Bosshard, P.P., Wiedemeier, D.B., Bichsel, D., R\u00fccker, M., and Stadlinger, B. (2019). Change of saliva composition with radiotherapy. Arch. Oral Biol., 106.","DOI":"10.1016\/j.archoralbio.2019.104480"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"208","DOI":"10.3389\/fimmu.2019.00208","article-title":"Oral Mucosal Epithelial Cells","volume":"10","author":"Groeger","year":"2019","journal-title":"Front. Immunol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1804249","DOI":"10.1080\/21688370.2020.1804249","article-title":"IL-1beta strengthens the physical barrier in gingival epithelial cells","volume":"8","author":"Stolte","year":"2020","journal-title":"Tissue Barriers"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"959","DOI":"10.1016\/j.ijrobp.2016.08.047","article-title":"Salivary Cytokine Levels and Oral Mucositis in Head and Neck Cancer Patients Treated With Chemotherapy and Radiation Therapy","volume":"96","author":"Bossi","year":"2016","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1007\/s00280-008-0732-8","article-title":"Is the pathobiology of chemotherapy-induced alimentary tract mucositis influenced by the type of mucotoxic drug administered?","volume":"63","author":"Logan","year":"2009","journal-title":"Cancer Chemother. Pharmacol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1007\/s13167-019-00163-4","article-title":"Innate immunity and oral microbiome: A personalized, predictive, and preventive approach to the management of oral diseases","volume":"10","author":"Yu","year":"2019","journal-title":"EPMA J."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1111\/j.1601-0825.2006.01254.x","article-title":"Histomorphometry and immunohistochemical features of grade I (WHO) oral radiomucositis","volume":"13","author":"Bonan","year":"2007","journal-title":"Oral Dis."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Homa-Mlak, I., Brzozowska, A., Mlak, R., Szudy-Szczyrek, A., and Ma\u0142ecka-Massalska, T. (2021). Neutrophil-to-Lymphocyte Ratio as a Factor Predicting Radiotherapy Induced Oral Mucositis in Head Neck Cancer Patients Treated with Radiotherapy. J. Clin. Med., 10.","DOI":"10.3390\/jcm10194444"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1038\/nri2800","article-title":"Innate IL-17-producing cells: The sentinels of the immune system","volume":"10","author":"Cua","year":"2010","journal-title":"Nat. Rev. Immunol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"687627","DOI":"10.3389\/fimmu.2021.687627","article-title":"Tissue Damage in Radiation-Induced Oral Mucositis Is Mitigated by IL-17 Receptor Signaling","volume":"12","author":"Dillon","year":"2021","journal-title":"Front. Immunol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"606","DOI":"10.1016\/j.chom.2016.10.001","article-title":"IL-17 Receptor Signaling in Oral Epithelial Cells Is Critical for Protection against Oropharyngeal Candidiasis","volume":"20","author":"Conti","year":"2016","journal-title":"Cell Host Microbe"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"i36","DOI":"10.1093\/jac\/dkp081","article-title":"The changing face of febrile neutropenia-from monotherapy to moulds to mucositis. Mucositis: From febrile neutropenia to febrile mucositis","volume":"63","author":"Blijlevens","year":"2009","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1101\/SQB.1989.054.01.003","article-title":"Approaching the asymptote? Evolution and revolution in immunology","volume":"54","author":"Janeway","year":"1989","journal-title":"Cold Spring Harb. Symp. Quant. Biol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1016\/j.it.2015.12.003","article-title":"Integration of Innate Immune Signaling","volume":"37","author":"Thaiss","year":"2016","journal-title":"Trends Immunol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1038\/nature18847","article-title":"The microbiome and innate immunity","volume":"535","author":"Thaiss","year":"2016","journal-title":"Nature"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"598","DOI":"10.1002\/path.3009","article-title":"Severity of doxorubicin-induced small intestinal mucositis is regulated by the TLR-2 and TLR-9 pathways","volume":"226","author":"Kaczmarek","year":"2012","journal-title":"J. Pathol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"877","DOI":"10.1002\/jcp.29976","article-title":"Site-specific contribution of Toll-like receptor 4 to intestinal homeostasis and inflammatory disease","volume":"236","author":"Bruning","year":"2021","journal-title":"J. Cell. Physiol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1376","DOI":"10.1158\/1535-7163.MCT-15-0990","article-title":"Irinotecan-Induced Gastrointestinal Dysfunction and Pain Are Mediated by Common TLR4-Dependent Mechanisms","volume":"15","author":"Wardill","year":"2016","journal-title":"Mol. Cancer Ther."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1044","DOI":"10.1016\/j.cell.2020.02.041","article-title":"Toll-like Receptors and the Control of Immunity","volume":"180","author":"Fitzgerald","year":"2020","journal-title":"Cell"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"672395","DOI":"10.1155\/2010\/672395","article-title":"DAMPening inflammation by modulating TLR signalling","volume":"2010","author":"Piccinini","year":"2010","journal-title":"Mediat. Inflamm."},{"key":"ref_51","first-page":"1961","article-title":"TLR4 gene in the regulation of periodontitis and its molecular mechanism","volume":"18","author":"Qi","year":"2019","journal-title":"Exp. Ther. Med."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"645","DOI":"10.18821\/0869-2084-2020-65-10-645-648","article-title":"Expression of toll-like and adhesive receptors on epithelial cells of the oral mucosa in periodontitis","volume":"65","author":"Lukova","year":"2020","journal-title":"Klin Lab Diagn"},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Ji, L., Hao, S., Wang, J., Zou, J., and Wang, Y. (2022). Roles of Toll-Like Receptors in Radiotherapy- and Chemotherapy-Induced Oral Mucositis: A Concise Review. Front. Cell. Infect. Microbiol., 12.","DOI":"10.3389\/fcimb.2022.831387"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"857","DOI":"10.1111\/jop.12298","article-title":"TLR2, TLR4 and CD86 gene polymorphisms in recurrent aphthous stomatitis","volume":"44","author":"Karasneh","year":"2015","journal-title":"J. Oral Pathol. Med."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1016\/j.archoralbio.2013.11.007","article-title":"The expression of hBDs in the gingival tissue and keratinocytes from healthy subjects and periodontitis patients","volume":"59","author":"Liu","year":"2014","journal-title":"Arch. Oral Biol."},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Shang, L., Deng, D., Buskermolen, J.K., Roffel, S., Janus, M.M., Krom, B.P., Crielaard, W., and Gibbs, S. (2019). Commensal and Pathogenic Biofilms Alter Toll-Like Receptor Signaling in Reconstructed Human Gingiva. Front. Cell. Infect. Microbiol., 9.","DOI":"10.3389\/fcimb.2019.00282"},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Hug, H., Mohajeri, M.H., and La Fata, G. (2018). Toll-Like Receptors: Regulators of the Immune Response in the Human Gut. Nutrients, 10.","DOI":"10.3390\/nu10020203"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1111\/jop.12152","article-title":"The role of oral flora in the development of chemotherapy-induced oral mucositis","volume":"44","author":"Stringer","year":"2015","journal-title":"J. Oral Pathol. Med."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1177\/0022034516641890","article-title":"Host-Microbiome Cross-talk in Oral Mucositis","volume":"95","author":"Vasconcelos","year":"2016","journal-title":"J. Dent. Res."},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Yamanobe, H., Yamamoto, K., Kishimoto, S., Nakai, K., Oseko, F., Yamamoto, T., Mazda, O., and Kanamura, N. (2023). Anti-Inflammatory Effects of beta-Cryptoxanthin on 5-Fluorouracil-Induced Cytokine Expression in Human Oral Mucosal Keratinocytes. Molecules, 28.","DOI":"10.3390\/molecules28072935"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1070","DOI":"10.1038\/s41385-019-0132-x","article-title":"Regulation of HMGB1 release protects chemoradiotherapy-associated mucositis","volume":"12","author":"Im","year":"2019","journal-title":"Mucosal Immunol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1080\/1744666X.2023.2182291","article-title":"The interaction between innate immunity and oral microbiota in oral diseases","volume":"19","author":"He","year":"2023","journal-title":"Expert Rev. Clin. Immunol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1016\/j.it.2005.06.004","article-title":"NLRs join TLRs as innate sensors of pathogens","volume":"26","author":"Martinon","year":"2005","journal-title":"Trends Immunol."},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Wei, J., Wang, H., Wang, H., Wang, B., Meng, L., Xin, Y., and Jiang, X. (2019). The role of NLRP3 inflammasome activation in radiation damage. Biomed. Pharmacother., 118.","DOI":"10.1016\/j.biopha.2019.109217"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"678","DOI":"10.1038\/s41580-020-0270-8","article-title":"Emerging connectivity of programmed cell death pathways and its physiological implications","volume":"21","author":"Bedoui","year":"2020","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1007\/s00520-022-07559-5","article-title":"Baseline gut microbiota composition is associated with oral mucositis and tumour recurrence in patients with head and neck cancer: A pilot study","volume":"31","author":"Bowen","year":"2023","journal-title":"Support. Care Cancer"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1097\/SPC.0000000000000202","article-title":"Toll-like receptors in the pathogenesis of chemotherapy-induced gastrointestinal toxicity","volume":"10","author":"Cario","year":"2016","journal-title":"Curr. Opin. Support. Palliat. Care"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1111\/odi.12224","article-title":"Microbiota and their role in the pathogenesis of oral mucositis","volume":"21","author":"Vanhoecke","year":"2015","journal-title":"Oral Dis."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"E337","DOI":"10.1073\/pnas.1614926114","article-title":"GAS6 is a key homeostatic immunological regulator of host-commensal interactions in the oral mucosa","volume":"114","author":"Nassar","year":"2017","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1419","DOI":"10.1111\/cmi.12127","article-title":"Commensal bacteria-dependent select expression of CXCL2 contributes to periodontal tissue homeostasis","volume":"15","author":"Zenobia","year":"2013","journal-title":"Cell. Microbiol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"690","DOI":"10.1007\/s12185-020-02958-y","article-title":"An analysis of oral microbial flora by T-RFLP in patients undergoing hematopoietic stem cell transplantation","volume":"112","author":"Takahashi","year":"2020","journal-title":"Int. J. Hematol."},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Mojdami, Z.D., Barbour, A., Oveisi, M., Sun, C., Fine, N., Saha, S., Marks, C., Elebyary, O., Watson, E., and Tenenbaum, H. (2022). The Effect of Intensity-Modulated Radiotherapy to the Head and Neck Region on the Oral Innate Immune Response and Oral Microbiome: A Prospective Cohort Study of Head and Neck Tumour Patients. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23179594"},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"Bruno, J.S., Al-Qadami, G.H., Laheij, A.M.G.A., Bossi, P., Fregnani, E.R., and Wardill, H.R. (2023). From Pathogenesis to Intervention: The Importance of the Microbiome in Oral Mucositis. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24098274"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1534","DOI":"10.3389\/fphys.2018.01534","article-title":"Mouse Microbiota Models: Comparing Germ-Free Mice and Antibiotics Treatment as Tools for Modifying Gut Bacteria","volume":"9","author":"Kennedy","year":"2018","journal-title":"Front. Physiol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"881949","DOI":"10.3389\/froh.2022.881949","article-title":"Oral-Gut Microbiome Axis in the Pathogenesis of Cancer Treatment-Induced Oral Mucositis","volume":"3","author":"Bowen","year":"2022","journal-title":"Front. Oral Health"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"374","DOI":"10.1016\/j.chom.2014.02.006","article-title":"Gut microbiota promote hematopoiesis to control bacterial infection","volume":"15","author":"Khosravi","year":"2014","journal-title":"Cell Host Microbe"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1249288","DOI":"10.1126\/science.1249288","article-title":"Microbiota-dependent crosstalk between macrophages and ILC3 promotes intestinal homeostasis","volume":"343","author":"Mortha","year":"2014","journal-title":"Science"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1002\/JLB.3RI0917-378R","article-title":"Interactions between the microbiota and innate and innate-like lymphocytes","volume":"103","author":"Constantinides","year":"2018","journal-title":"J. Leukoc. Biol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"2445","DOI":"10.31557\/APJCP.2023.24.7.2445","article-title":"Prophylaxis of Oral Mucositis with Iodine Solution during Concurrent Chemoradiation of Head and Neck Cancer: Preliminary Results of a Double-Blind, Randomized Controlled Trial","volume":"24","author":"Namuangchan","year":"2023","journal-title":"Asian Pac. J. Cancer Prev."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1053\/jhin.2002.1391","article-title":"Do cancer patients with chemotherapy-induced leukopenia benefit from an antiseptic chlorhexidine-based oral rinse? A double-blind, block-randomized, controlled study","volume":"53","author":"Pitten","year":"2003","journal-title":"J. Hosp. Infect."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1016\/0030-4220(89)90321-6","article-title":"Effect of chlorhexidine rinsing on the oropharyngeal ecology in patients with head and neck cancer who have irradiation mucositis","volume":"67","author":"Spijkervet","year":"1989","journal-title":"Oral Surg. Oral Med. Oral Pathol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"1012","DOI":"10.1038\/sj.bjc.6600824","article-title":"Oral mucositis and selective elimination of oral flora in head and neck cancer patients receiving radiotherapy: A double-blind randomised clinical trial","volume":"88","author":"Stokman","year":"2003","journal-title":"Br. J. Cancer"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1016\/S0360-3016(01)01444-4","article-title":"Mucositis reduction by selective elimination of oral flora in irradiated cancers of the head and neck: A placebo-controlled double-blind randomized study","volume":"50","author":"Wijers","year":"2001","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"104559","DOI":"10.1016\/j.oraloncology.2019.104559","article-title":"The effectiveness of probiotics in prevention and treatment of cancer therapy-induced oral mucositis: A systematic review and meta-analysis","volume":"102","author":"Shu","year":"2020","journal-title":"Oral Oncol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"1935","DOI":"10.21873\/anticanres.13303","article-title":"Lactobacillus brevis CD2 for Prevention of Oral Mucositis in Patients With Head and Neck Tumors: A Multicentric Randomized Study","volume":"39","author":"Belgioia","year":"2019","journal-title":"Anticancer Res."},{"key":"ref_86","doi-asserted-by":"crossref","unstructured":"Mazziotta, C., Tognon, M., Martini, F., Torreggiani, E., and Rotondo, J.C. (2023). Probiotics Mechanism of Action on Immune Cells and Beneficial Effects on Human Health. Cells, 12.","DOI":"10.3390\/cells12010184"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"5898","DOI":"10.1016\/j.csbj.2021.10.028","article-title":"Oral microbiota transplantation fights against head and neck radiotherapy-induced oral mucositis in mice","volume":"19","author":"Xiao","year":"2021","journal-title":"Comput. Struct. Biotechnol. J."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/j.ebiom.2017.02.002","article-title":"The Potential Effect of Oral Microbiota in the Prediction of Mucositis During Radiotherapy for Nasopharyngeal Carcinoma","volume":"18","author":"Zhu","year":"2017","journal-title":"EBioMedicine"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1016\/j.ijrobp.2011.05.055","article-title":"Toll-like receptor 5 agonist protects mice from dermatitis and oral mucositis caused by local radiation: Implications for head-and-neck cancer radiotherapy","volume":"83","author":"Burdelya","year":"2012","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"839467","DOI":"10.3389\/fvets.2022.839467","article-title":"Clinical evaluation of toll-like receptor-5 agonist for radiation-induced oral mucositis in beagle dogs","volume":"9","author":"Ko","year":"2022","journal-title":"Front. Vet. Sci."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1080\/1547691X.2019.1699617","article-title":"KMRC011, an agonist of toll-like receptor 5, mitigates irradiation-induced tissue damage and mortality in cynomolgus monkeys","volume":"17","author":"Lee","year":"2020","journal-title":"J. Immunotoxicol."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1111\/jpi.12191","article-title":"Melatonin blunts the mitochondrial\/NLRP3 connection and protects against radiation-induced oral mucositis","volume":"58","author":"Ortiz","year":"2015","journal-title":"J. Pineal Res."},{"key":"ref_93","doi-asserted-by":"crossref","unstructured":"Pulsipher, A., Savage, J.R., Kennedy, T.P., Gupta, K., Cuiffo, B.G., Sonis, S.T., and Lee, W.Y. (2021). GM-1111 reduces radiation-induced oral mucositis in mice by targeting pattern recognition receptor-mediated inflammatory signaling. PLoS ONE, 16.","DOI":"10.1371\/journal.pone.0249343"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1016\/j.btre.2017.05.002","article-title":"Dusquetide: Reduction in oral mucositis associated with enduring ancillary benefits in tumor resolution and decreased mortality in head and neck cancer patients","volume":"15","author":"Kudrimoti","year":"2017","journal-title":"Biotechnol. Rep."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"655","DOI":"10.1111\/j.1601-0825.2010.01671.x","article-title":"Attenuation of radiation- and chemoradiation-induced mucositis using gamma-D-glutamyl-L-tryptophan (SCV-07)","volume":"16","author":"Watkins","year":"2010","journal-title":"Oral Dis."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1538\/expanim.19-0057","article-title":"Effects of anakinra on the small intestine mucositis induced by methotrexate in rats","volume":"69","author":"Ozcicek","year":"2020","journal-title":"Exp. Anim."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1111\/bcpt.13851","article-title":"Anakinra and dexamethasone treatment of idarubicin-induced mucositis and diarrhoea in rats","volume":"132","author":"Kullenberg","year":"2023","journal-title":"Basic Clin. Pharmacol. Toxicol."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"6803","DOI":"10.1038\/s41598-022-10700-3","article-title":"Supporting the gastrointestinal microenvironment during high-dose chemotherapy and stem cell transplantation by inhibiting IL-1 signaling with anakinra","volume":"12","author":"Wardill","year":"2022","journal-title":"Sci. Rep."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"948","DOI":"10.1186\/s13063-020-04847-5","article-title":"Anakinra: Efficacy in the management of fever during neutropenia and mucositis in autologous stem cell transplantation (AFFECT-2)-study protocol for a multicenter randomized double-blind placebo-controlled trial","volume":"21","author":"Biemond","year":"2020","journal-title":"Trials"},{"key":"ref_100","doi-asserted-by":"crossref","unstructured":"Chen, K.-J., Chen, Y.-L., Ueng, S.-H., Hwang, T.-L., Kuo, L.-M., and Hsieh, P.-W. (2021). Neutrophil elastase inhibitor (MPH-966) improves intestinal mucosal damage and gut microbiota in a mouse model of 5-fluorouracil-induced intestinal mucositis. Biomed. Pharmacother., 134.","DOI":"10.1016\/j.biopha.2020.111152"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"2994","DOI":"10.1002\/1878-0261.12851","article-title":"Targeting immunogenic cell death in cancer","volume":"14","author":"Ahmed","year":"2020","journal-title":"Mol. Oncol."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"2872","DOI":"10.1200\/JCO.2018.79.0006","article-title":"Impact of Baseline Steroids on Efficacy of Programmed Cell Death-1 and Programmed Death-Ligand 1 Blockade in Patients With Non-Small-Cell Lung Cancer","volume":"36","author":"Arbour","year":"2018","journal-title":"J. Clin. Oncol."},{"key":"ref_103","doi-asserted-by":"crossref","unstructured":"von Itzstein, M.S., Gonugunta, A.S., Sheffield, T., Homsi, J., Dowell, J.E., Koh, A.Y., Raj, P., Fattah, F., Wang, Y., and Basava, V.S. (2022). Association between Antibiotic Exposure and Systemic Immune Parameters in Cancer Patients Receiving Checkpoint Inhibitor Therapy. Cancers, 14.","DOI":"10.3390\/cancers14051327"},{"key":"ref_104","doi-asserted-by":"crossref","unstructured":"Petrelli, F., Iaculli, A., Signorelli, D., Ghidini, A., Dottorini, L., Perego, G., Ghidini, M., Zaniboni, A., Gori, S., and Inno, A. (2020). Survival of Patients Treated with Antibiotics and Immunotherapy for Cancer: A Systematic Review and Meta-Analysis. J. Clin. Med., 9.","DOI":"10.20944\/preprints202003.0425.v1"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"971","DOI":"10.1126\/science.1240537","article-title":"The intestinal microbiota modulates the anticancer immune effects of cyclophosphamide","volume":"342","author":"Viaud","year":"2013","journal-title":"Science"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"967","DOI":"10.1126\/science.1240527","article-title":"Commensal bacteria control cancer response to therapy by modulating the tumor microenvironment","volume":"342","author":"Iida","year":"2013","journal-title":"Science"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/22\/16314\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T21:22:54Z","timestamp":1760131374000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/22\/16314"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,11,14]]},"references-count":106,"journal-issue":{"issue":"22","published-online":{"date-parts":[[2023,11]]}},"alternative-id":["ijms242216314"],"URL":"https:\/\/doi.org\/10.3390\/ijms242216314","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,11,14]]}}}