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2000
Volume 21, Issue 3
  • ISSN: 1573-3947
  • E-ISSN: 1875-6301

Abstract

Background

Immunotherapy is a promising addition to the cancer treatment arsenal, with the potential to be an effective adjuvant therapy. In the ever-changing landscape of cancer care, it appears as a potential fourth pillar, supplementing surgery, chemotherapy, and radiation. The key to effective immunotherapy is cautious patient selection, which is based on a thorough study of the unique immune makeup of each patient. This review article aims to provide a comprehensive understanding of the fundamental principles of tumor immunity and immunotherapy, with a specific focus on oral squamous cell carcinoma.

Methods

The review involved a thorough investigation of scientific databases and relevant publications, including studies conducted up to the present date obtained from PubMed, Science Direct, and Google Scholar Key. The selected studies underwent careful evaluation for methodological rigor and the significance of their findings.

Results

Checkpoint inhibitors, targeted monoclonal antibodies, adoptive cell transfer, cancer vaccines, biomarkers and prediction tools, and cytokine immunotherapy are all promising treatments for oral cancer.

Conclusion

In recent decades, there has been a substantial increase in interest and study in cancer immunotherapy, indicating a turning point in our approach to cancer treatment. While significant progress has been made, major hurdles remain across a range of cancers.

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2024-04-18
2025-09-04
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References

  1. SenevirathnaK. JayawickramaS.M. JayasingheY.A. PrabaniK.I.P. AkshalaK. PradeepR.G.G.R. DamayanthiH.D.W.T. HettiarachchiK. DorjiT. Lucero-PrisnoD.E. RajapakseR.M.G. KanmodiK.K. JayasingheR.D. Nanoplatforms: The future of oral cancer treatment.Health Sci. Rep.202368e147110.1002/hsr2.147137547360
    [Google Scholar]
  2. D.K.Awasthi DixitA. Oral cancer–nicotine and alcohol.Clinical and Laboratory Research, BioRes Scientia Publishers.20231210.59657/clr.brs.23.007
    [Google Scholar]
  3. WongT.S.C. WiesenfeldD. Oral cancer.Aust. Dent. J.201863S1S91S9910.1111/adj.1259429574808
    [Google Scholar]
  4. SiegelR.L. MillerK.D. WagleN.S. JemalA. Cancer statistics, 2023.CA Cancer J. Clin.2023731174810.3322/caac.2176336633525
    [Google Scholar]
  5. SoniV. Mucoadhesive film for local delivery to oral cancer: Formulation development, box–behnken experimental design, and in vitro characterization.Asian J. Pharm.2022164
    [Google Scholar]
  6. GuptaB. BrayF. KumarN. JohnsonN.W. Associations between oral hygiene habits, diet, tobacco and alcohol and risk of oral cancer: A case–control study from India.Cancer Epidemiol.20175171410.1016/j.canep.2017.09.00328968558
    [Google Scholar]
  7. ZipfelP.F. SkerkaC. From magic bullets to modern therapeutics: Paul Ehrlich, the German immunobiologist and physician coined the term ‘complement’.Mol. Immunol.2022150909810.1016/j.molimm.2022.08.00236027818
    [Google Scholar]
  8. HendersonE.A. LukomskiS. BooneB.A. Emerging applications of cancer bacteriotherapy towards treatment of pancreatic cancer.Front. Oncol.202313121709510.3389/fonc.2023.121709537588093
    [Google Scholar]
  9. AbbasA.K. LichtmanA.H. PillaiS. Cellular and molecular immunity.Philadelphia, PAElsevier/Saunders2012
    [Google Scholar]
  10. AhrendsT. BusselaarJ. SeversonT.M. BąbałaN. de VriesE. BovensA. WesselsL. van LeeuwenF. BorstJ. CD4+ T cell help creates memory CD8+ T cells with innate and help-independent recall capacities.Nat. Commun.2019101553110.1038/s41467‑019‑13438‑131797935
    [Google Scholar]
  11. KimS.K. ChoS.W. The evasion mechanisms of cancer immunity and drug intervention in the tumor microenvironment.Front. Pharmacol.20221386869510.3389/fphar.2022.86869535685630
    [Google Scholar]
  12. McKenzieK. MiltonM. SmithG. Ouellette-KuntzH. Systematic review of the prevalence and incidence of intellectual disabilities: Current trends and issues.Curr. Dev. Disord. Rep.20163210411510.1007/s40474‑016‑0085‑7
    [Google Scholar]
  13. PrimeS.S. CirilloN. CheongS.C. PrimeM.S. ParkinsonE.K. Targeting the genetic landscape of oral potentially malignant disorders has the potential as a preventative strategy in oral cancer.Cancer Lett.202151810211410.1016/j.canlet.2021.05.02534139286
    [Google Scholar]
  14. GeissL.S. WangJ. ChengY.J. ThompsonT.J. BarkerL. LiY. AlbrightA.L. GreggE.W. Prevalence and incidence trends for diagnosed diabetes among adults aged 20 to 79 years, United States, 1980-2012.JAMA2014312121218122610.1001/jama.2014.1149425247518
    [Google Scholar]
  15. BorseV. KonwarA.N. BuragohainP. Oral cancer diagnosis and perspectives in India.Sens Int2020110004610.1016/j.sintl.2020.10004634766046
    [Google Scholar]
  16. KawakitaD. MatsuoK. Alcohol and head and neck cancer.Cancer Metastasis Rev.201736342543410.1007/s10555‑017‑9690‑028815324
    [Google Scholar]
  17. Prawdzic SeńkowskaA. KiczmerP. StrzelczykJ.K. KowalskiD. KrakowczykŁ. OstrowskaZ. Impact of HPV infection on gene expression and methylation in oral cancer patients.J. Med. Microbiol.201968344044510.1099/jmm.0.00089830624179
    [Google Scholar]
  18. KumarM. NanavatiR. ModiT. DobariyaC. Oral cancer: Etiology and risk factors: A review.J. Cancer Res. Ther.201612245846310.4103/0973‑1482.18669627461593
    [Google Scholar]
  19. NigamK. SamadiF.M. SrivastavaS. MohammadS. SanyalS. Smoking and XPC gene polymorphism interact to modulate the risk of oral cancer.J. Maxillofac. Oral Surg.202120460761110.1007/s12663‑020‑01340‑z34776693
    [Google Scholar]
  20. ReidyJ. McHughE. StassenL.F.A. A review of the relationship between alcohol and oral cancer.Surgeon20119527828310.1016/j.surge.2011.01.01021843823
    [Google Scholar]
  21. OgdenG.R. Alcohol and oral cancer.Alcohol200535316917310.1016/j.alcohol.2005.04.00216054978
    [Google Scholar]
  22. RavascoP. Nutrition in cancer patients.J. Clin. Med.201988121110.3390/jcm808121131416154
    [Google Scholar]
  23. ThompsonR. MitrouG. BrownS. Major new review of global evidence on diet, nutrition and physical activity: A blueprint to reduce cancer risk.Nutrition Bulletin43326928310.1111/nbu.12345
    [Google Scholar]
  24. SandL. JalouliJ. Viruses and oral cancer. Is there a link?Microbes Infect.201416537137810.1016/j.micinf.2014.02.00924613199
    [Google Scholar]
  25. SatimanE.A.F.E.N. AhmadH. RamziA.B. Abdul WahabR. KaderiM.A. Wan HarunW.H.A. DashperS. McCulloughM. ArzmiM.H. The role of Candida albicans candidalysin ECE1 gene in oral carcinogenesis.J. Oral Pathol. Med.202049983584110.1111/jop.1301432170981
    [Google Scholar]
  26. SalehiniyaH. RaeiM. Oral cavity and lip cancer in the world: An epidemiological review.Biomed. Res. Ther.2020783898390510.15419/bmrat.v7i8.619
    [Google Scholar]
  27. WarnakulasuriyaS. KerrA.R. Oral cancer screening: Past, present, and future.J. Dent. Res.2021100121313132010.1177/0022034521101479534036828
    [Google Scholar]
  28. AlsahafiE. BeggK. AmelioI. RaulfN. LucarelliP. SauterT. TavassoliM. Clinical update on head and neck cancer: Molecular biology and ongoing challenges.Cell Death Dis.201910854010.1038/s41419‑019‑1769‑931308358
    [Google Scholar]
  29. AdorisioS. ArgentieriM.P. AvatoP. CaderniG. ChioccioliS. CirmiS. DelfinoD.V. GrecoG. HreliaP. IritiM. LenziM. LombardoG.E. LuceriC. MaugeriA. MontopoliM. MuscariI. NaniM.F. NavarraM. GasperiniS. TurriniE. FimognariC. The molecular basis of the anticancer properties of quercetin.Pharmadvances20213349652210.36118/pharmadvances.2021.10
    [Google Scholar]
  30. MarinJ.J.G. MaciasR.I.R. MonteM.J. RomeroM.R. AsensioM. Sanchez-MartinA. Cives-LosadaC. TempranoA.G. Espinosa-EscuderoR. ReviejoM. BohorquezL.H. BrizO. Molecular bases of drug resistance in hepatocellular carcinoma.Cancers2020126166310.3390/cancers1206166332585893
    [Google Scholar]
  31. LechnerM. LiuJ. MastersonL. FentonT.R. HPV-associated oropharyngeal cancer: Epidemiology, molecular biology and clinical management.Nat. Rev. Clin. Oncol.202219530632710.1038/s41571‑022‑00603‑735105976
    [Google Scholar]
  32. GotwalsP. CameronS. CipollettaD. CremascoV. CrystalA. HewesB. MuellerB. QuaratinoS. Sabatos-PeytonC. PetruzzelliL. EngelmanJ.A. DranoffG. Prospects for combining targeted and conventional cancer therapy with immunotherapy.Nat. Rev. Cancer201717528630110.1038/nrc.2017.1728338065
    [Google Scholar]
  33. TanS. LiD. ZhuX. Cancer immunotherapy: Pros, cons and beyond.Biomed. Pharmacother.202012410982110.1016/j.biopha.2020.10982131962285
    [Google Scholar]
  34. YamashitaK. ArimotoA. NishiM. TanakaT. FujitaM. FukuokaE. SugitaY. NakagawaA. HasegawaH. SuzukiS. KakejiY. Application of iNKT cell-targeted active immunotherapy in cancer treatment.Anticancer Res.20183874233423910.21873/anticanres.1271929970556
    [Google Scholar]
  35. MohanS. BhaskaranM. GeorgeA. ThirutheriA. SomasundaranM. PavithranA. Immunotherapy in oral cancer.J. Pharm. Bioallied Sci.201911610710.4103/JPBS.JPBS_31_1931198321
    [Google Scholar]
  36. OsipovA. MurphyA. ZhengL. From immune checkpoints to vaccines: The past, present and future of cancer immunotherapy.Adv. Cancer Res.20191436314410.1016/bs.acr.2019.03.00231202363
    [Google Scholar]
  37. KujanO. van SchaijikB. FarahC.S. Immune checkpoint inhibitors in oral cavity squamous cell carcinoma and oral potentially malignant disorders: A systematic review.Cancers2020127193710.3390/cancers1207193732708945
    [Google Scholar]
  38. GaronE.B. RizviN.A. HuiR. LeighlN. BalmanoukianA.S. EderJ.P. PatnaikA. AggarwalC. GubensM. HornL. CarcerenyE. AhnM.J. FelipE. LeeJ.S. HellmannM.D. HamidO. GoldmanJ.W. SoriaJ.C. Dolled-FilhartM. RutledgeR.Z. ZhangJ. LuncefordJ.K. RangwalaR. LubinieckiG.M. RoachC. EmancipatorK. GandhiL. KEYNOTE-001 Investigators Pembrolizumab for the treatment of non-small-cell lung cancer.N. Engl. J. Med.2015372212018202810.1056/NEJMoa150182425891174
    [Google Scholar]
  39. NakamuraY. NamikawaK. YoshikawaS. KiniwaY. MaekawaT. YamasakiO. IseiT. MatsushitaS. NomuraM. NakaiY. FukushimaS. SaitoS. TakenouchiT. TanakaR. KatoH. OtsukaA. MatsuyaT. BabaN. NagaseK. InozumeT. FujimotoN. KuwatsukaY. OnishiM. KanekoT. OnumaT. UmedaY. OgataD. TakahashiA. OtsukaM. TeramotoY. YamazakiN. Anti-PD-1 antibody monotherapy versus anti-PD-1 plus anti-CTLA-4 combination therapy as first-line immunotherapy in unresectable or metastatic mucosal melanoma: A retrospective, multicenter study of 329 Japanese cases (JMAC study).ESMO Open20216610032510.1016/j.esmoop.2021.10032534839104
    [Google Scholar]
  40. LarkinJ. Chiarion-SileniV. GonzalezR. GrobJ.J. CoweyC.L. LaoC.D. SchadendorfD. DummerR. SmylieM. RutkowskiP. FerrucciP.F. HillA. WagstaffJ. CarlinoM.S. HaanenJ.B. MaioM. Marquez-RodasI. McArthurG.A. AsciertoP.A. LongG.V. CallahanM.K. PostowM.A. GrossmannK. SznolM. DrenoB. BastholtL. YangA. RollinL.M. HorakC. HodiF.S. WolchokJ.D. Combined nivolumab and ipilimumab or monotherapy in untreated melanoma.N. Engl. J. Med.20153731233410.1056/NEJMoa150403026027431
    [Google Scholar]
  41. KrcikE.M. Radiation therapy plus anti-programmed death ligand 1 immunotherapy: A review on overall survival.Radiol. Technol.201688112312827601709
    [Google Scholar]
  42. BlankC.U. EnkA. Therapeutic use of anti-CTLA-4 antibodies.Int. Immunol.201527131010.1093/intimm/dxu07625038057
    [Google Scholar]
  43. HoW.J. MehraR. Pembrolizumab for the treatment of head and neck squamous cell cancer.Expert Opin. Biol. Ther.201919987988510.1080/14712598.2019.164431531317798
    [Google Scholar]
  44. SinghS. KumarN.K. DwiwediP. CharanJ. KaurR. SidhuP. ChughV.K. Monoclonal antibodies: A review.Curr. Clin. Pharmacol.2018132859910.2174/157488471266617080912472828799485
    [Google Scholar]
  45. UribeM.L. MarroccoI. YardenY. EGFR in cancer: Signaling mechanisms, drugs, and acquired resistance.Cancers20211311274810.3390/cancers1311274834206026
    [Google Scholar]
  46. PerisanidisC. Prevalence of EGFR tyrosine kinase domain mutations in head and neck squamous cell carcinoma: Cohort study and systematic review.In Vivo2017311233410.21873/invivo.1102028064216
    [Google Scholar]
  47. CaiW.Q. ZengL.S. WangL.F. WangY.Y. ChengJ.T. ZhangY. HanZ.W. ZhouY. HuangS.L. WangX.W. PengX.C. XiangY. MaZ. CuiS.Z. XinH.W. The latest battles between EGFR monoclonal antibodies and resistant tumor cells.Front. Oncol.202010124910.3389/fonc.2020.0124932793499
    [Google Scholar]
  48. LiL. DengL. MengX. GuC. MengL. LiK. ZhangX. MengY. XuW. ZhaoL. ChenJ. ZhuZ. HuangH. Tumor-targeting anti-EGFR x anti-PD1 bispecific antibody inhibits EGFR-overexpressing tumor growth by combining EGFR blockade and immune activation with direct tumor cell killing.Transl. Oncol.202114110091610.1016/j.tranon.2020.10091633129108
    [Google Scholar]
  49. HwangL.A. PhangB.H. LiewO.W. IqbalJ. KohX.H. KohX.Y. OthmanR. XueY. RichardsA.M. LaneD.P. SabapathyK. Monoclonal antibodies against specific p53 hotspot mutants as potential tools for precision medicine.Cell Rep.201822129931210.1016/j.celrep.2017.11.11229298430
    [Google Scholar]
  50. ChasovV. ZaripovM. MirgayazovaR. KhadiullinaR. ZmievskayaE. GaneevaI. ValiullinaA. RizvanovA. BulatovE. Promising new tools for targeting p53 mutant cancers: Humoral and cell-based immunotherapies.Front. Immunol.20211270773410.3389/fimmu.2021.70773434484205
    [Google Scholar]
  51. RosenbergS.A. RestifoN.P. Adoptive cell transfer as personalized immunotherapy for human cancer.Science20153486230626810.1126/science.aaa496725838374
    [Google Scholar]
  52. LiD. LiX. ZhouW.L. HuangY. LiangX. JiangL. YangX. SunJ. LiZ. HanW.D. WangW. Genetically engineered T cells for cancer immunotherapy.Signal Transduct. Target. Ther.2019413510.1038/s41392‑019‑0070‑931637014
    [Google Scholar]
  53. PrietoP.A. DurflingerK.H. WunderlichJ.R. RosenbergS.A. DudleyM.E. Enrichment of CD8+ cells from melanoma tumor-infiltrating lymphocyte cultures reveals tumor reactivity for use in adoptive cell therapy.J. Immunother.20103351547
    [Google Scholar]
  54. CurranK.J. PegramH.J. BrentjensR.J. Chimeric antigen receptors for T cell immunotherapy: Current understanding and future directions.J. Gene Med.201214640541510.1002/jgm.260422262649
    [Google Scholar]
  55. ParkJ.H. BrentjensR.J. Are all chimeric antigen receptors created equal?J. Clin. Oncol.201533665165310.1200/JCO.2014.57.547225605860
    [Google Scholar]
  56. KlebanoffC.A. RosenbergS.A. RestifoN.P. Prospects for gene-engineered T cell immunotherapy for solid cancers.Nat. Med.2016221263610.1038/nm.401526735408
    [Google Scholar]
  57. BlassE. OttP.A. Advances in the development of personalized neoantigen-based therapeutic cancer vaccines.Nat. Rev. Clin. Oncol.202118421522910.1038/s41571‑020‑00460‑233473220
    [Google Scholar]
  58. WangR. PanW. JinL. HuangW. LiY. WuD. GaoC. MaD. LiaoS. Human papillomavirus vaccine against cervical cancer: Opportunity and challenge.Cancer Lett.20204718810210.1016/j.canlet.2019.11.03931812696
    [Google Scholar]
  59. HamdyS. HaddadiA. HungR.W. LavasanifarA. Targeting dendritic cells with nano-particulate PLGA cancer vaccine formulations.Adv. Drug Deliv. Rev.20116310-1194395510.1016/j.addr.2011.05.02121679733
    [Google Scholar]
  60. ChiangC. CoukosG. KandalaftL. Whole tumor antigen vaccines: Where are we?Vaccines20153234437210.3390/vaccines302034426343191
    [Google Scholar]
  61. SaxenaM. BhardwajN. Re-emergence of dendritic cell vaccines for cancer treatment.Trends Cancer20184211913710.1016/j.trecan.2017.12.00729458962
    [Google Scholar]
  62. FaghfuriE. PourfarziF. FaghfouriA.H. ShadbadMA. HajiasgharzadehK. BaradaranB. Recent developments of RNA-based vaccines in cancer immunotherapy.Expert Opin. Biol. Ther.202121220121810.1080/14712598.2020.181570432842798
    [Google Scholar]
  63. KorbelikM. Optimization of whole tumor cell vaccines by interaction with phagocytic receptors.Vaccines20219890410.3390/vaccines908090434452029
    [Google Scholar]
  64. WaldmannT.A. Cytokines in cancer immunotherapy.Cold Spring Harb. Perspect. Biol.20181012a02847210.1101/cshperspect.a02847229101107
    [Google Scholar]
  65. de Abreu CostaL. OttoniM.H.E. Dos SantosM.G. MeirelesA. Gomes de AlmeidaV. de Fátima PereiraW. Alves de Avelar-FreitasB. Eustáquio Alvim Brito-MeloG. Dimethyl sulfoxide (DMSO) decreases cell proliferation and TNF-α, IFN-γ, and IL-2 cytokines production in cultures of peripheral blood lymphocytes.Molecules20172211178910.3390/molecules2211178929125561
    [Google Scholar]
  66. TarhiniA.A. GogasH. KirkwoodJ.M. IFN-α in the treatment of melanoma.J. Immunol.201218983789379310.4049/jimmunol.129006023042723
    [Google Scholar]
  67. MacDonaldA. WuT.C. HungC.F. Interleukin 2-based fusion proteins for the treatment of cancer.J. Immunol. Res.2021202111110.1155/2021/785580834790830
    [Google Scholar]
  68. McFarlaneA. PohlerE. MoragaI. Molecular and cellular factors determining the functional pleiotropy of cytokines.FEBS J.2023290102525255210.1111/febs.1642035246947
    [Google Scholar]
  69. NaveO. ShorY. BarR. SegalE.E. SigronM. A new treatment for breast cancer using a combination of two drugs: AZD9496 and palbociclib.Sci. Rep.2024141130710.1038/s41598‑023‑48305‑z38225243
    [Google Scholar]
  70. WebsterR.M. Combination therapies in oncology.Nat. Rev. Drug Discov.2016152818210.1038/nrd.2016.326837588
    [Google Scholar]
  71. LüL. LiuX. WangC. HuF. WangJ. HuangH. Dissociation of E-cadherin/β-catenin complex by MG132 and bortezomib enhances CDDP induced cell death in oral cancer SCC-25 cells.Toxicol. In Vitro 20152981965197610.1016/j.tiv.2015.07.00826165741
    [Google Scholar]
  72. ZhengZ. WangX. ChenD. Proteasome inhibitor MG132 enhances the sensitivity of human OSCC cells to cisplatin via a ROS/DNA damage/p53 axis.Exp. Ther. Med.202325522410.3892/etm.2023.1192437123203
    [Google Scholar]
  73. HaradaK. FerdousT. UeyamaY. Gimeracil exerts radiosensitizing effects on oral squamous cell carcinoma cells in vitro and in vivo.Anticancer Res.201636115923593010.21873/anticanres.1117927793917
    [Google Scholar]
  74. HaradaK. FerdousT. HaradaT. TakenawaT. UeyamaY. Gimeracil enhances the antitumor effect of cisplatin in oral squamous cell carcinoma cells in vitro and in vivo. Oncol. Lett.20171433349335610.3892/ol.2017.660228927087
    [Google Scholar]
  75. ChoiJ-H. LeeM.H. ChoY.J. ParkB.S. KimS. KimG.C. The bacterial protein azurin enhances sensitivity of oral squamous carcinoma cells to anticancer drugs.Yonsei Med. J.201152577377810.3349/ymj.2011.52.5.77321786442
    [Google Scholar]
  76. NalejskaE. MączyńskaE. LewandowskaM.A. Prognostic and predictive biomarkers: Tools in personalized oncology.Mol. Diagn. Ther.201418327328410.1007/s40291‑013‑0077‑924385403
    [Google Scholar]
  77. JørgensenJ.T. Predictive biomarkers and clinical evidence.Basic Clin. Pharmacol. Toxicol.2021128564264810.1111/bcpt.1357833665955
    [Google Scholar]
  78. MonteiroL. MelloF.W. WarnakulasuriyaS. Tissue biomarkers for predicting the risk of oral cancer in patients diagnosed with oral leukoplakia: A systematic review.Oral Dis.20212781977199210.1111/odi.1374733290585
    [Google Scholar]
  79. MirghaniH. Lang KuhsK.A. WaterboerT. Biomarkers for early identification of recurrences in HPV-driven oropharyngeal cancer.Oral Oncol.20188210811410.1016/j.oraloncology.2018.05.01529909884
    [Google Scholar]
  80. AllgäuerM. BudcziesJ. ChristopoulosP. EndrisV. LierA. RempelE. VolckmarA.L. KirchnerM. von WinterfeldM. LeichsenringJ. NeumannO. FröhlingS. PenzelR. ThomasM. SchirmacherP. StenzingerA. Implementing tumor mutational burden (TMB) analysis in routine diagnostics—a primer for molecular pathologists and clinicians.Transl. Lung Cancer Res.20187570371510.21037/tlcr.2018.08.1430505715
    [Google Scholar]
  81. NaikP.P. DasD.N. PandaP.K. MukhopadhyayS. SinhaN. PraharajP.P. AgarwalR. BhutiaS.K. Implications of cancer stem cells in developing therapeutic resistance in oral cancer.Oral Oncol.20166212213510.1016/j.oraloncology.2016.10.00827865365
    [Google Scholar]
  82. LaskarS.G. BasuT. GuptaT. BudrukkarA. MurthyV. AgarwalJ. Toxicity with radiotherapy for oral cancers and its management: A practical approach.J. Cancer Res. Ther.2012867210.4103/0973‑1482.9221922322736
    [Google Scholar]
  83. DranitsarisG. ZhuX. AdunlinG. VincentM.D. Cost effectiveness vs. affordability in the age of immuno-oncology cancer drugs.Expert Rev. Pharmacoecon. Outcomes Res.201818435135710.1080/14737167.2018.146727029681201
    [Google Scholar]
  84. KimD. LiR. Contemporary treatment of locally advanced oral cancer.Curr. Treat. Options Oncol.20192043210.1007/s11864‑019‑0631‑830874958
    [Google Scholar]
  85. El-SayesN. VitoA. MossmanK. Tumor heterogeneity: A great barrier in the age of cancer immunotherapy.Cancers202113480610.3390/cancers1304080633671881
    [Google Scholar]
  86. DrakeC. Combination immunotherapy approaches.Ann Oncol.2012238414610.1093/annonc/mds262
    [Google Scholar]
  87. EmensL.A. AsciertoP.A. DarcyP.K. DemariaS. EggermontA.M.M. RedmondW.L. SeligerB. MarincolaF.M. Cancer immunotherapy: Opportunities and challenges in the rapidly evolving clinical landscape.Eur. J. Cancer20178111612910.1016/j.ejca.2017.01.03528623775
    [Google Scholar]
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