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development of head and neck squamous cell carcinoma (HNSCC). Treatment with immune checkpoint inhibitors targeting programmed death 1 (PD-1) or its ligand PD-L1 has shown poor efficacy in HNSCC patients, observing only a 20\u201330% response. Therefore, biological marker identification associated with PD-1 blockade response is important to improve prognosis and define novel therapeutics for HNSCC patients. Therapy response was associated with increased frequencies of activated CD27+T cells, activated CD79a+ B cells, antigen-presenting CD74+ dendritic and B cells, and PD-L1+ and PD-L2+ myeloid-derived suppressor cells (MDSCs). The oral microbiota composition differed significantly in mice bearing tongue tumors and treated with anti-PD-1. A higher abundance of Allobaculum, Blautia, Faecalibacterium, Dorea, or Roseburia\u00a0was associated with response to the therapy. However, an increase in Enterococcus was attributed to tongue tumor-bearing non-responding mice. Our findings indicate that differences in immune phenotypes, protein expression, and bacterial abundance occur as mice develop tongue tumors and are treated with anti-PD-1. These results may have a clinical impact as specific bacteria and immune phenotype could serve as biomarkers for treatment response in HNSCC.<\/jats:p>","DOI":"10.3390\/cancers16112065","type":"journal-article","created":{"date-parts":[[2024,5,30]],"date-time":"2024-05-30T03:45:08Z","timestamp":1717040708000},"page":"2065","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Immune and Microbial Signatures Associated with PD-1 Blockade Sensitivity in a Preclinical Model for HPV+ Oropharyngeal Cancer"],"prefix":"10.3390","volume":"16","author":[{"given":"Jennifer","family":"D\u00edaz-Rivera","sequence":"first","affiliation":[{"name":"Cancer Biology Division, Comprehensive Cancer Center, University of Puerto Rico, San Juan, PR 00936, USA"},{"name":"Microbiology and Medical Zoology Department, University of Puerto Rico Medical Sciences Campus, San Juan, PR 00936, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael A.","family":"Rodr\u00edguez-Rivera","sequence":"additional","affiliation":[{"name":"Cancer Biology Division, Comprehensive Cancer Center, University of Puerto Rico, San Juan, PR 00936, USA"},{"name":"Microbiology and Medical Zoology Department, University of Puerto Rico Medical Sciences Campus, San Juan, PR 00936, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1538-7557","authenticated-orcid":false,"given":"Natalie M.","family":"Mel\u00e9ndez-V\u00e1zquez","sequence":"additional","affiliation":[{"name":"Microbiology and Medical Zoology Department, University of Puerto Rico Medical Sciences Campus, San Juan, PR 00936, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1880-0498","authenticated-orcid":false,"given":"Filipa","family":"Godoy-Vitorino","sequence":"additional","affiliation":[{"name":"Microbiology and Medical Zoology Department, University of Puerto Rico Medical Sciences Campus, San Juan, PR 00936, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie M.","family":"Dorta-Estremera","sequence":"additional","affiliation":[{"name":"Cancer Biology Division, Comprehensive Cancer Center, University of Puerto Rico, San Juan, PR 00936, USA"},{"name":"Microbiology and Medical Zoology Department, University of Puerto Rico Medical Sciences Campus, San Juan, PR 00936, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,5,30]]},"reference":[{"key":"ref_1","first-page":"299","article-title":"HPV in oropharyngeal cancer: The basics to know in clinical practice","volume":"34","author":"Elrefaey","year":"2014","journal-title":"Acta Otorhinolaryngol. Ital."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"209","DOI":"10.3322\/caac.21660","article-title":"Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries","volume":"71","author":"Sung","year":"2021","journal-title":"CA Cancer J. Clin."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Guo, K., Xiao, W., Chen, X., Zhao, Z., Lin, Y., and Chen, G. (2021). Epidemiological Trends of Head and Neck Cancer: A Population-Based Study. BioMed Res. Int., 2021.","DOI":"10.1155\/2021\/1738932"},{"key":"ref_4","first-page":"175","article-title":"Incidence of oral cavity and pharyngeal cancers by anatomical sites in population-based registries in Puerto Rico and the United States of America","volume":"32","author":"Ortiz","year":"2013","journal-title":"P. R. Health Sci. J."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1186\/s13027-016-0095-4","article-title":"HPV-16 infection modifies overall survival of Puerto Rican HNSCC patients","volume":"11","year":"2016","journal-title":"Infect. Agents Cancer"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2125","DOI":"10.1002\/cncr.31322","article-title":"Head and neck squamous cell cancers in the United States are rare and the risk now is higher among white individuals compared with black individuals","volume":"124","author":"Fakhry","year":"2018","journal-title":"Cancer"},{"key":"ref_7","first-page":"F1000","article-title":"Recent advances in the understanding and management of oropharyngeal cancer","volume":"7","author":"Hay","year":"2018","journal-title":"F1000Research"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"306","DOI":"10.1038\/s41571-022-00603-7","article-title":"HPV-associated oropharyngeal cancer: Epidemiology, molecular biology and clinical management","volume":"19","author":"Lechner","year":"2022","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1016\/j.cell.2019.08.012","article-title":"Proteomics of Melanoma Response to Immunotherapy Reveals Mitochondrial Dependence","volume":"179","author":"Harel","year":"2019","journal-title":"Cell"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"705096","DOI":"10.3389\/fimmu.2021.705096","article-title":"Anti\u2013PD-1 and Anti\u2013PD-L1 in Head and Neck Cancer: A Network Meta-Analysis","volume":"12","author":"Botticelli","year":"2021","journal-title":"Front. Immunol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"662","DOI":"10.1002\/cam4.106","article-title":"PD-1 as a potential target in cancer therapy","volume":"2","author":"McDermott","year":"2013","journal-title":"Cancer Med."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"669587","DOI":"10.3389\/fmed.2021.669587","article-title":"Response to Immune Checkpoint Inhibitor Treatment in Advanced Cervical Cancer and Biomarker Study","volume":"8","author":"Shieh","year":"2021","journal-title":"Front. Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"364","DOI":"10.3389\/fimmu.2020.00364","article-title":"Characteristics of Tumor-Infiltrating Lymphocytes Prior to and During Immune Checkpoint Inhibitor Therapy","volume":"11","author":"Plesca","year":"2020","journal-title":"Front. Immunol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1038\/bjc.2013.639","article-title":"Tumour-infiltrating lymphocytes predict for outcome in HPV-positive oropharyngeal cancer","volume":"110","author":"Ward","year":"2014","journal-title":"Br. J. Cancer"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1589","DOI":"10.1038\/s41416-022-01708-7","article-title":"Tumour-infiltrating lymphocytes in oropharyngeal cancer: A validation study according to the criteria of the International Immuno-Oncology Biomarker Working Group","volume":"126","author":"Almangush","year":"2022","journal-title":"Br. J. Cancer"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Pang, X., Fan, H.Y., Tang, Y.L., Wang, S.S., Cao, M.X., Wang, H.F., Dai, L.L., Wang, K., Yu, X.H., and Wu, J.B. (2020). Myeloid derived suppressor cells contribute to the malignant progression of oral squamous cell carcinoma. PLoS ONE, 15.","DOI":"10.1371\/journal.pone.0229089"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2175","DOI":"10.1084\/jem.20100637","article-title":"Upregulation of Tim-3 and PD-1 expression is associated with tumor antigen\u2013specific CD8+ T cell dysfunction in melanoma patients","volume":"207","author":"Fourcade","year":"2010","journal-title":"J. Exp. Med."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2046","DOI":"10.1172\/JCI80445","article-title":"TIGIT and PD-1 impair tumor antigen\u2013specific CD8+ T cells in melanoma patients","volume":"125","author":"Chauvin","year":"2015","journal-title":"J. Clin. Investig."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Aghamajidi, A., and Vareki, S.M. (2022). The Effect of the Gut Microbiota on Systemic and Anti-Tumor Immunity and Response to Systemic Therapy against Cancer. Cancers, 14.","DOI":"10.3390\/cancers14153563"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1378","DOI":"10.1016\/j.jtho.2019.04.007","article-title":"The Diversity of Gut Microbiome is Associated With Favorable Responses to Anti-Programmed Death 1 Immunotherapy in Chinese Patients With NSCLC","volume":"14","author":"Jin","year":"2019","journal-title":"J. Thorac. Oncol."},{"key":"ref_21","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_22","doi-asserted-by":"crossref","first-page":"1084","DOI":"10.1126\/science.aac4255","article-title":"Commensal Bifidobacterium promotes antitumor immunity and facilitates anti-PD-L1 efficacy","volume":"350","author":"Sivan","year":"2015","journal-title":"Science"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s00394-018-1703-4","article-title":"The role of the microbiome for human health: From basic science to clinical applications","volume":"57","author":"Mohajeri","year":"2018","journal-title":"Eur. J. Nutr."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"591088","DOI":"10.3389\/fimmu.2020.591088","article-title":"The Oral Microbiome and Cancer","volume":"11","author":"Irfan","year":"2020","journal-title":"Front. Immunol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"110931","DOI":"10.18632\/oncotarget.20677","article-title":"High-resolution microbiome profiling uncovers Fusobacterium nucleatum, Lactobacillus gasseri\/johnsonii, and Lactobacillus vaginalis associated to oral and oropharyngeal cancer in saliva from HPV positive and HPV negative patients treated with surgery and chemo-radiation","volume":"8","author":"White","year":"2017","journal-title":"Oncotarget"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"51320","DOI":"10.18632\/oncotarget.9710","article-title":"16S rRNA amplicon sequencing identifies microbiota associated with oral cancer, human papilloma virus infection and surgical treatment","volume":"7","author":"Jedlicka","year":"2016","journal-title":"Oncotarget"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"100813","DOI":"10.1016\/j.neo.2022.100813","article-title":"Fusobacterium is enriched in oral cancer and promotes induction of programmed death-ligand 1 (PD-L1)","volume":"31","author":"Michikawa","year":"2022","journal-title":"Neoplasia"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"911","DOI":"10.1002\/hed.21040","article-title":"Preclinical models of HPV+ and HPV\u2212 HNSCC in mice: An immune clearance of HPV+ HNSCC","volume":"31","author":"Williams","year":"2009","journal-title":"Head Neck"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1186\/s40425-019-0728-4","article-title":"Targeting interferon signaling and CTLA-4 enhance the therapeutic efficacy of anti-PD-1 immunotherapy in preclinical model of HPV+ oral cancer","volume":"7","author":"Hegde","year":"2019","journal-title":"J. Immunother. Cancer"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"852","DOI":"10.1038\/s41587-019-0209-9","article-title":"Reproducible, interactive, scalable and extensible microbiome data science using QIIME 2","volume":"37","author":"Bolyen","year":"2019","journal-title":"Nat. Biotechnol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"D590","DOI":"10.1093\/nar\/gks1219","article-title":"The SILVA ribosomal RNA gene database project: Improved data processing and web-based tools","volume":"41","author":"Quast","year":"2013","journal-title":"Nucleic Acids Res."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"7188","DOI":"10.1093\/nar\/gkm864","article-title":"SILVA: A comprehensive online resource for quality checked and aligned ribosomal RNA sequence data compatible with ARB","volume":"35","author":"Pruesse","year":"2007","journal-title":"Nucleic Acids Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"W310","DOI":"10.1093\/nar\/gkad407","article-title":"MicrobiomeAnalyst 2.0: Comprehensive statistical, functional and integrative analysis of microbiome data","volume":"51","author":"Lu","year":"2023","journal-title":"Nucleic Acids Res."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Segata, N., Izard, J., Waldron, L., Gevers, D., Miropolsky, L., Garrett, W.S., and Huttenhower, C. (2011). Metagenomic biomarker discovery and explanation. Genome Biol., 12.","DOI":"10.1186\/gb-2011-12-s1-p47"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1145724","DOI":"10.3389\/fonc.2023.1145724","article-title":"B cells as modulators of HPV+ oropharyngeal cancer in a preclinical model","volume":"13","year":"2023","journal-title":"Front. Oncol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"17898","DOI":"10.1038\/s41598-021-95738-5","article-title":"Comparative effects of alive and pasteurized Akkermansia muciniphila on normal diet-fed mice","volume":"11","author":"Ashrafian","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1002\/ame2.12257","article-title":"Characteristics of gut microbiota in representative mice strains: Implications for biological research","volume":"5","author":"Guo","year":"2022","journal-title":"Anim. Model. Exp. Med."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"17461","DOI":"10.1038\/s41598-022-22356-0","article-title":"Peripheral T cell cytotoxicity predicts the efficacy of anti-PD-1 therapy for advanced non-small cell lung cancer patients","volume":"12","author":"Iwahori","year":"2022","journal-title":"Sci. Rep."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"773168","DOI":"10.3389\/fimmu.2021.773168","article-title":"What Happens to the Immune Microenvironment After PD-1 Inhibitor Therapy?","volume":"12","author":"Wang","year":"2021","journal-title":"Front. Immunol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"2692","DOI":"10.3389\/fimmu.2018.02692","article-title":"Defining Memory CD8 T Cell","volume":"9","author":"Martin","year":"2018","journal-title":"Front. Immunol."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Portale, F., and Di Mitri, D. (2023). NK Cells in Cancer: Mechanisms of Dysfunction and Therapeutic Potential. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24119521"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/j.coi.2021.09.005","article-title":"The role of CD4 T cells in rejection of solid tumors","volume":"74","author":"Poncette","year":"2022","journal-title":"Curr. Opin. Immunol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1038\/nature11824","article-title":"T-helper-1-cell cytokines drive cancer into senescence","volume":"494","author":"Wieder","year":"2013","journal-title":"Nature"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"637","DOI":"10.1084\/jem.20091918","article-title":"Tumor-reactive CD4+ T cells develop cytotoxic activity and eradicate large established melanoma after transfer into lymphopenic hosts","volume":"207","author":"Quezada","year":"2010","journal-title":"J. Exp. Med."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"778","DOI":"10.1002\/hed.26534","article-title":"Immune checkpoint expression in HNSCC patients before and after definitive chemoradiotherapy","volume":"43","author":"Doescher","year":"2021","journal-title":"Head Neck"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1007\/s13238-020-00707-9","article-title":"Memory T cells: Strategies for optimizing tumor immunotherapy","volume":"11","author":"Liu","year":"2020","journal-title":"Protein Cell"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1038\/ni889","article-title":"Lineage relationship and protective immunity of memory CD8 T cell subsets","volume":"4","author":"Wherry","year":"2003","journal-title":"Nat. Immunol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1269","DOI":"10.1016\/j.bbamcr.2016.03.026","article-title":"The multifaceted roles of the invariant chain CD74\u2014More than just a chaperone","volume":"1863","year":"2016","journal-title":"Biochim. Biophys. Acta (BBA)\u2014Mol. Cell Res."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"12255","DOI":"10.1038\/srep12255","article-title":"Regulatory B cells preferentially accumulate in tumor-draining lymph nodes and promote tumor growth","volume":"5","author":"Ganti","year":"2015","journal-title":"Sci. Rep."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/j.molimm.2020.01.008","article-title":"PD-L1+ regulatory B cells act as a T cell suppressor in a PD-L1-dependent manner in melanoma patients with bone metastasis","volume":"119","author":"Wu","year":"2020","journal-title":"Mol. Immunol."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Zhang, E., Ding, C., Li, S., Zhou, X., Aikemu, B., Fan, X., Sun, J., Zheng, M., and Yang, X. (2023). Roles and mechanisms of tumour-infiltrating B cells in human cancer: A new force in immunotherapy. Biomark. Res., 11.","DOI":"10.1186\/s40364-023-00460-1"},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Yao, S., Huang, Z., Wei, C., Wang, Y., Xiao, H., Chen, S., and Huang, Z. (2023). CD79A work as a potential target for the prognosis of patients with OSCC: Analysis of immune cell infiltration in oral squamous cell carcinoma based on the CIBERSORTx deconvolution algorithm. BMC Oral Health, 23.","DOI":"10.1186\/s12903-023-02936-w"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"111572","DOI":"10.1016\/j.celrep.2022.111572","article-title":"CD74 as a regulator of transcription in normal B cells","volume":"41","author":"David","year":"2022","journal-title":"Cell Rep."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"3016","DOI":"10.1158\/1078-0432.CCR-15-2226","article-title":"Inflammatory Marker Testing Identifies CD74 Expression in Melanoma Tumor Cells, and Its Expression Associates with Favorable Survival for Stage III Melanoma","volume":"22","author":"Ekmekcioglu","year":"2016","journal-title":"Clin. Cancer Res."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1186\/s12967-023-04151-1","article-title":"The potential crosstalk between tumor and plasma cells and its association with clinical outcome and immunotherapy response in bladder cancer","volume":"21","author":"Long","year":"2023","journal-title":"J. Transl. Med."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1016\/j.coi.2018.09.012","article-title":"Natural regulatory plasma cells","volume":"55","author":"Fillatreau","year":"2018","journal-title":"Curr. Opin. Immunol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"20332","DOI":"10.1002\/cam4.6619","article-title":"Immunomodulatory properties of CD38 antibodies and their effect on anticancer efficacy in multiple myeloma","volume":"12","author":"Bisht","year":"2023","journal-title":"Cancer Med."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1186\/s12943-022-01657-y","article-title":"Myeloid-derived suppressor cells: An emerging target for anticancer immunotherapy","volume":"21","author":"Wu","year":"2022","journal-title":"Mol. Cancer"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"413","DOI":"10.21037\/tlcr.2019.08.09","article-title":"The association of PD-L1 expression with the efficacy of anti-PD-1\/PD-L1 immunotherapy and survival of non-small cell lung cancer patients: A meta-analysis of randomized controlled trials","volume":"8","author":"Xu","year":"2019","journal-title":"Transl. Lung Cancer Res."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1770","DOI":"10.21037\/apm-19-670","article-title":"The efficacy and safety comparison of PD-1\/PD-L1 antibody, chemotherapy and supportive treatment for pretreated advanced esophagogastric cancer: A network meta-analysis","volume":"9","author":"Liu","year":"2020","journal-title":"Ann. Palliat. Med."},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Stojanov, S., Berlec, A., and \u0160trukelj, B. (2020). The Influence of Probiotics on the Firmicutes\/Bacteroidetes Ratio in the Treatment of Obesity and Inflammatory Bowel disease. Microorganisms, 8.","DOI":"10.3390\/microorganisms8111715"},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Rizzardi, K.F., Indiani, C.M.D.S.P., Mattos-Graner, R.D.O., De Sousa, E.T., Nobre-dos-Santos, M., and Parisotto, T.M. (2021). Firmicutes Levels in the Mouth Reflect the Gut Condition With Respect to Obesity and Early Childhood Caries. Front. Cell. Infect. Microbiol., 11.","DOI":"10.3389\/fcimb.2021.593734"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"948068","DOI":"10.3389\/fonc.2022.948068","article-title":"Oral microbiota in oropharyngeal cancers: Friend or foe?","volume":"12","author":"Nocini","year":"2022","journal-title":"Front. Oncol."},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Schmidt, B.L., Kuczynski, J., Bhattacharya, A., Huey, B., Corby, P.M., Queiroz, E.L.S., Nightingale, K., Kerr, A.R., DeLacure, M.D., and Veeramachaneni, R. (2014). Changes in Abundance of Oral Microbiota Associated with Oral Cancer. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0098741"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1279837","DOI":"10.3389\/fimmu.2023.1279837","article-title":"Interactions between neutrophils and T-helper 17 cells","volume":"14","author":"Fan","year":"2023","journal-title":"Front. Immunol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1038\/s41423-018-0004-4","article-title":"When worlds collide: Th17 and Treg cells in cancer and autoimmunity","volume":"15","author":"Knochelmann","year":"2018","journal-title":"Cell. Mol. Immunol."},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Renaude, E., Kroemer, M., Loyon, R., Binda, D., Borg, C., Guittaut, M., Hervouet, E., and Peixoto, P. (2020). The Fate of Th17 Cells is Shaped by Epigenetic Modifications and Remodeled by the Tumor Microenvironment. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21051673"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"e340","DOI":"10.1038\/emm.2017.36","article-title":"Microbiota in T-cell homeostasis and inflammatory diseases","volume":"49","author":"Lee","year":"2017","journal-title":"Exp. Mol. Med."},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Lu, J., Jin, X., Yang, S., Li, Y., Wang, X., and Wu, M. (2022). Immune mechanism of gut microbiota and its metabolites in the occurrence and development of cardiovascular diseases. Front. Microbiol., 13.","DOI":"10.3389\/fmicb.2022.1034537"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1158200","DOI":"10.3389\/fimmu.2023.1158200","article-title":"Gut microbiota-derived short-chain fatty acids regulate gastrointestinal tumor immunity: A novel therapeutic strategy?","volume":"14","author":"Dong","year":"2023","journal-title":"Front. Immunol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"988","DOI":"10.1016\/j.cmet.2021.03.002","article-title":"Gut microbial metabolites facilitate anticancer therapy efficacy by modulating cytotoxic CD8+ T cell immunity","volume":"33","author":"He","year":"2021","journal-title":"Cell Metab."},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Komiyama, E.Y., Lepesqueur, L.S.S., Yassuda, C.G., Samaranayake, L.P., Parahitiyawa, N.B., Balducci, I., and Koga-Ito, C.Y. (2016). Enterococcus Species in the Oral Cavity: Prevalence, Virulence Factors and Antimicrobial Susceptibility. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0163001"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1186\/s12967-023-03929-7","article-title":"Enterococcus faecalis promotes the progression of colorectal cancer via its metabolite: Biliverdin","volume":"21","author":"Zhang","year":"2023","journal-title":"J. Transl. Med."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"2932","DOI":"10.1016\/j.jmb.2019.05.030","article-title":"Dr. Jekyll and Mr. Hide: How Enterococcus faecalis Subverts the Host Immune Response to Cause Infection","volume":"431","author":"Kao","year":"2019","journal-title":"J. Mol. Biol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"2671","DOI":"10.4049\/jimmunol.0804012","article-title":"Monocyte Chemoattractant Protein-1 Contributes to Gut Homeostasis and Intestinal Inflammation by Composition of IL-10\u2013Producing Regulatory Macrophage Subset","volume":"184","author":"Takada","year":"2010","journal-title":"J. Immunol."},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"Molina, M.A., D\u00edaz, A.M., Hesse, C., Ginter, W., Gentilini, M.V., Nu\u00f1ez, G.G., Canellada, A.M., Sparwasser, T., Berod, L., and Castro, M.S. (2015). Immunostimulatory Effects Triggered by Enterococcus faecalis CECT7121 Probiotic Strain Involve Activation of Dendritic Cells and Interferon-Gamma Production. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0127262"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"2160","DOI":"10.1128\/IAI.67.5.2160-2165.1999","article-title":"Survival of Enterococcus faecalis in Mouse Peritoneal Macrophages","volume":"67","author":"Pikis","year":"1999","journal-title":"Infect. Immun."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"6160","DOI":"10.1038\/s41467-023-41817-2","article-title":"Repressed Blautia-acetate immunological axis underlies breast cancer progression promoted by chronic stress","volume":"14","author":"Ye","year":"2023","journal-title":"Nat. Commun."},{"key":"ref_79","doi-asserted-by":"crossref","unstructured":"Singh, V., Lee, G., Son, H., Koh, H., Kim, E.S., Unno, T., and Shin, J.H. (2023). Butyrate producers, \u201cThe Sentinel of Gut\u201d: Their intestinal significance with and beyond butyrate, and prospective use as microbial therapeutics. Front. Microbiol., 13.","DOI":"10.3389\/fmicb.2022.1103836"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"848","DOI":"10.1016\/j.neo.2017.08.004","article-title":"Metagenomic shotgun sequencing and unbiased metabolomic profiling identify specific human gut microbiota and metabolites associated with immune checkpoint therapy efficacy in melanoma patients","volume":"19","author":"Frankel","year":"2017","journal-title":"Neoplasia"},{"key":"ref_81","first-page":"1569","article-title":"Propionate of a microbiota metabolite induces cell apoptosis and cell cycle arrest in lung cancer","volume":"20","author":"Kim","year":"2019","journal-title":"Mol. Med. Rep."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1126\/science.aan3706","article-title":"Gut microbiome influences efficacy of PD-1\u2013based immunotherapy against epithelial tumors","volume":"359","author":"Routy","year":"2018","journal-title":"Science"},{"key":"ref_83","doi-asserted-by":"crossref","unstructured":"Grenda, A., Iwan, E., Krawczyk, P., Fr\u0105k, M., Chmielewska, I., Bomba, A., Giza, A., Rolska-Kopi\u0144ska, A., Szczyrek, M., and Kieszko, R. (2022). Attempting to Identify Bacterial Allies in Immunotherapy of NSCLC Patients. Cancers, 14.","DOI":"10.3390\/cancers14246250"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"934695","DOI":"10.3389\/fimmu.2022.934695","article-title":"Akkermansia muciniphila and Gut Immune System: A Good Friendship That Attenuates Inflammatory Bowel Disease, Obesity, and Diabetes","volume":"13","author":"Rodrigues","year":"2022","journal-title":"Front. Immunol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"1383","DOI":"10.1038\/s12276-020-0473-2","article-title":"Of men in mice: The development and application of a humanized gnotobiotic mouse model for microbiome therapeutics","volume":"52","author":"Park","year":"2020","journal-title":"Exp. Mol. Med."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1126\/science.aaw4361","article-title":"Laboratory mice born to wild mice have natural microbiota and model human immune responses","volume":"365","author":"Rosshart","year":"2019","journal-title":"Science"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"23176","DOI":"10.1038\/s41598-021-02638-9","article-title":"Oral microbiome associated with lymph node metastasis in oral squamous cell carcinoma","volume":"11","author":"Eun","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1186\/s12935-022-02554-6","article-title":"Microbial and molecular differences according to the location of head and neck cancers","volume":"22","author":"Kim","year":"2022","journal-title":"Cancer Cell Int."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1128\/mSystems.00323-19","article-title":"The Oral Mouse Microbiome Promotes Tumorigenesis in Oral Squamous Cell Carcinoma","volume":"4","author":"Stashenko","year":"2019","journal-title":"mSystems"},{"key":"ref_90","doi-asserted-by":"crossref","unstructured":"Abusleme, L., Hong, B.-Y., Hoare, A., Konkel, J.E., Diaz, P.I., and Moutsopoulos, N.M. (2017). Oral Microbiome Characterization in Murine Models. Bio-Protocol, 7.","DOI":"10.21769\/BioProtoc.2655"},{"key":"ref_91","doi-asserted-by":"crossref","unstructured":"Hajishengallis, G. (2023). Illuminating the oral microbiome and its host interactions: Animal models of disease. FEMS Microbiol. Rev., 47.","DOI":"10.1093\/femsre\/fuad018"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"101305","DOI":"10.1016\/j.smim.2019.101305","article-title":"Lymphocyte-activation gene 3 (LAG3): The next immune checkpoint receptor","volume":"42","author":"Ruffo","year":"2019","journal-title":"Semin. Immunol."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"1198365","DOI":"10.3389\/fimmu.2023.1198365","article-title":"Current understanding of CTLA-4: From mechanism to autoimmune diseases","volume":"14","author":"Hossen","year":"2023","journal-title":"Front. Immunol."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"1895","DOI":"10.1038\/s12276-023-00985-3","article-title":"Double-edged sword: \u03b3\u03b4 T cells in mucosal homeostasis and disease","volume":"55","author":"Kang","year":"2023","journal-title":"Exp. Mol. Med."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"665","DOI":"10.6004\/jnccn.2011.0055","article-title":"The Epidemic of HPV-Associated Oropharyngeal Cancer Is Here: Is It Time to Change Our Treatment Paradigms?","volume":"9","author":"Sturgis","year":"2011","journal-title":"J. Natl. Compr. Cancer Netw."}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/16\/11\/2065\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T14:50:43Z","timestamp":1760107843000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/16\/11\/2065"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,5,30]]},"references-count":95,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2024,6]]}},"alternative-id":["cancers16112065"],"URL":"https:\/\/doi.org\/10.3390\/cancers16112065","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,5,30]]}}}