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2000
Volume 25, Issue 4
  • ISSN: 1566-5232
  • E-ISSN: 1875-5631

Abstract

Lung cancer is a leading cause of mortality worldwide. Immunotherapy has emerged as a potentially effective strategy, as traditional medicines have shown minimal success. This review investigates the current state of immunotherapy for lung cancer treatment, focusing on its mechanisms, clinical applications, strategies, and future directions. This study focuses on the different characteristics of non-small and small-cell lung cancer to emphasize the need for targeted treatment strategies. In non-small cell lung cancer, immune checkpoint inhibitors that target PD-1, PD-L1, and CTLA-4 have shown a strong therapeutic benefit and increased survival rates. The complex interactions among tumor cells, immune cells, and the tumor microenvironment significantly impact the outcome of immunotherapy. The determination of predicting biomarkers and conquering resistance requires an understanding of the tumor microenvironment. This study addresses a range of immunotherapeutic strategies, such as immune modulators, monoclonal antibodies, and cancer vaccines. The combination approaches are being explored to enhance treatment effectiveness and address resistance mechanisms that integrate immunotherapy with other modalities. Despite advancements, challenges still exist. The identification of reliable biomarkers, regulating immune-related adverse effects, and the overcoming of limitations in treating metastatic disease require more investigation. Future research directions should include exploring the immune microenvironment, developing personalized treatment strategies based on tumor profiles, and integrating new technologies for patient screening. Immunotherapy holds immense potential to modify lung cancer treatment and enhance clinical results.

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2025-01-06
2025-10-15
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References

  1. LiuW Ganoderma triterpenoids attenuate tumour angiogenesis in lung cancer tumour-bearing nude mice.Pharm Biol202058110701077
    [Google Scholar]
  2. PandiA MamoG GetachewD KitilaF KalappanV DhiravidamaniS. A brief review on lung cancer.IJPRHS201641907914
    [Google Scholar]
  3. XingP.Y. ZhuY.X. WangL. HuiZ.G. LiuS.M. RenJ.S. ZhangY. SongY. LiuC.C. HuangY.C. LiaoX.Z. XingX.J. WangD.B. YangL. DuL.B. LiuY.Q. ZhangY.Z. LiuY.Y. WeiD.H. ZhangK. ShiJ.F. QiaoY.L. ChenW.Q. LiJ.L. DaiM. LuCCRES Group What are the clinical symptoms and physical signs for non-small cell lung cancer before diagnosis is made? A nation-wide multicenter 10-year retrospective study in China.Cancer Med.2019884055406910.1002/cam4.225631150167
    [Google Scholar]
  4. LeeSH Chemotherapy for lung cancer in the era of personalized medicine.Tuberc Respir Dis (Seoul)2019823179189
    [Google Scholar]
  5. KimH.C. ChoiC.M. Current status of immunotherapy for lung cancer and future perspectives.Tuberc. Respir. Dis. (Seoul)2020831141910.4046/trd.2019.003931905428
    [Google Scholar]
  6. SiegelR.L. MillerK.D. JemalA. Cancer statistics, 2018.CA Cancer J. Clin.201868173010.3322/caac.2144229313949
    [Google Scholar]
  7. GonzalezH. HagerlingC. WerbZ. Roles of the immune system in cancer: From tumor initiation to metastatic progression.Genes Dev.20183219-201267128410.1101/gad.314617.11830275043
    [Google Scholar]
  8. MamdaniH. MatosevicS. KhalidA.B. DurmG. JalalS.I. Immunotherapy in lung cancer: Current landscape and future directions.Front. Immunol.20221382361810.3389/fimmu.2022.82361835222404
    [Google Scholar]
  9. RizviN.A. MazièresJ. PlanchardD. StinchcombeT.E. DyG.K. AntoniaS.J. HornL. LenaH. MinenzaE. MennecierB. OttersonG.A. CamposL.T. GandaraD.R. LevyB.P. NairS.G. ZalcmanG. WolfJ. SouquetP.J. BaldiniE. CappuzzoF. ChouaidC. DowlatiA. SanbornR. Lopez-ChavezA. GroheC. HuberR.M. HarbisonC.T. BaudeletC. LestiniB.J. RamalingamS.S. Activity and safety of nivolumab, an anti-PD-1 immune checkpoint inhibitor, for patients with advanced, refractory squamous non-small-cell lung cancer (CheckMate 063): A phase 2, single-arm trial.Lancet Oncol.201516325726510.1016/S1470‑2045(15)70054‑925704439
    [Google Scholar]
  10. StevenA FisherSA RobinsonBW Immunotherapy for lung cancer 2016; Respirology:2016215821833Available from: https://onlinelibrary.wiley.com/doi/full/10.1111/ resp.12789
    [Google Scholar]
  11. LahiriA Lung cancer immunotherapy: Progress, pitfalls, and promises.Mol Cancer202322140
    [Google Scholar]
  12. ArcaroA. Targeted therapies for small cell lung cancer: Where do we stand?Crit. Rev. Oncol. Hematol.201595215416410.1016/j.critrevonc.2015.03.00125800975
    [Google Scholar]
  13. ZhanX. FengS. ZhouX. LiaoW. ZhaoB. YangQ. TanQ. ShenJ. Immunotherapy response and microenvironment provide biomarkers of immunotherapy options for patients with lung adenocarcinoma.Front. Genet.202213104743510.3389/fgene.2022.104743536386793
    [Google Scholar]
  14. ChowA PericaK KlebanoffCA WolchokJD Clinical implications of T cell exhaustion for cancer immunotherapy.Nat Rev Clin Oncol2022Dec; 1912775790Epub 2022 Oct 10.10.1038/s41571‑022‑00689‑z36216928PMC10984554
    [Google Scholar]
  15. ArosC.J. PaulM.K. PantojaC.J. BishtB. MenesesL.K. VijayarajP. SandlinJ.M. FranceB. TseJ.A. ChenM.W. ShiaD.W. RickabaughT.M. DamoiseauxR. GompertsB.N. High-throughput drug screening identifies a potent wnt inhibitor that promotes airway basal stem cell Homeostasis.Cell Rep.202030720552064.e510.1016/j.celrep.2020.01.05932075752
    [Google Scholar]
  16. WangW. LiuH. LiG. What’s the difference between lung adenocarcinoma and lung squamous cell carcinoma? Evidence from a retrospective analysis in a cohort of Chinese patients.Front. Endocrinol. (Lausanne)20221394744310.3389/fendo.2022.94744336105402
    [Google Scholar]
  17. ZappaC MousaSA Non-small cell lung cancer: Current treatment and future advances.Transl Lung Cancer Res201653288300
    [Google Scholar]
  18. BordasA. CedilloJ.L. ArnalichF. Esteban-RodriguezI. Guerra-PastriánL. de CastroJ. Martín-SánchezC. AtienzaG. Fernández-CapitanC. RiosJ.J. MontielC. Expression patterns for nicotinic acetylcholine receptor subunit genes in smoking-related lung cancers.Oncotarget2017840678786789010.18632/oncotarget.1894828978081
    [Google Scholar]
  19. American society for radiation oncology (ASTRO)2024Available from: https://www.astro.org/
  20. PernotS. EvrardS. KhatibA.M. The give-and-take interaction between the tumor microenvironment and immune cells regulating tumor progression and repression.Front. Immunol.20221385085610.3389/fimmu.2022.85085635493456
    [Google Scholar]
  21. AltorkiN.K. MarkowitzG.J. GaoD. PortJ.L. SaxenaA. StilesB. McGrawT. MittalV. The lung microenvironment: An important regulator of tumour growth and metastasis.Nat. Rev. Cancer201919193110.1038/s41568‑018‑0081‑930532012
    [Google Scholar]
  22. StankovicB. BjørhovdeH.A.K. SkarshaugR. AamodtH. FrafjordA. MüllerE. HammarströmC. BerakiK. BækkevoldE.S. WoldbækP.R. HellandÅ. BrustugunO.T. ØynebråtenI. CorthayA. Immune cell composition in human non-small cell lung cancer.Front. Immunol.20199310110.3389/fimmu.2018.0310130774636
    [Google Scholar]
  23. BaiR. CuiJ. Development of immunotherapy strategies targeting tumor microenvironment is fiercely ongoing.Front. Immunol.20221389016610.3389/fimmu.2022.89016635833121
    [Google Scholar]
  24. HasegawaT. SuzukiH. YamauraT. MutoS. OkabeN. OsugiJ. HoshinoM. HiguchiM. IseK. GotohM. Prognostic value of peripheral and local forkhead box P3+ regulatory T cells in patients with non-small-cell lung cancer.Mol. Clin. Oncol.20142568569410.3892/mco.2014.29925054031
    [Google Scholar]
  25. KinoshitaT. IshiiG. HiraokaN. HirayamaS. YamauchiC. AokageK. HishidaT. YoshidaJ. NagaiK. OchiaiA. Forkhead box P3 regulatory T cells coexisting with cancer associated fibroblasts are correlated with a poor outcome in lung adenocarcinoma.Cancer Sci.2013104440941510.1111/cas.1209923305175
    [Google Scholar]
  26. LingY. WangJ. WangL. HouJ. QianP. Xiang-dongW. Roles of CEACAM1 in cell communication and signaling of lung cancer and other diseases.Cancer Metastasis Rev.201534234735710.1007/s10555‑015‑9569‑x26081722
    [Google Scholar]
  27. FridmanG. GrieserE. HillR. KhuddusN. BersaniT. SlonimC. Propranolol for the treatment of orbital infantile hemangiomas.Ophthal. Plast. Reconstr. Surg.201127319019410.1097/IOP.0b013e318201d34421283032
    [Google Scholar]
  28. MandlS.J. RountreeR.B. DalpozzoK. DoL. LombardoJ.R. SchoonmakerP.L. DirmeierU. SteigerwaldR. GiffonT. LausR. DelcayreA. Immunotherapy with MVA-BN®-HER2 induces HER-2-specific Th1 immunity and alters the intratumoral balance of effector and regulatory T cells.Cancer Immunol. Immunother.2012611192910.1007/s00262‑011‑1077‑421822917
    [Google Scholar]
  29. LahmarQ KeirsseJ LaouiD MovahediK Van OvermeireE Van GinderachterJA Tissue-resident versus monocyte-derived macrophages in the tumor microenvironment.Biochim Biophys Acta2016186512334
    [Google Scholar]
  30. AlmatroodiS.A. McDonaldC.F. DarbyI.A. PouniotisD.S. Characterization of M1/M2 tumour-associated Macrophages (TAMs) and Th1/Th2 cytokine profiles in patients with NSCLC.Cancer Microenviron.20169111110.1007/s12307‑015‑0174‑x26319408
    [Google Scholar]
  31. FridlenderZ.G. SunJ. KimS. KapoorV. ChengG. LingL. WorthenG.S. AlbeldaS.M. Polarization of tumor-associated neutrophil phenotype by TGF-β: “N1” versus “N2” TAN.Cancer Cell200916318319410.1016/j.ccr.2009.06.01719732719
    [Google Scholar]
  32. DavidC.J. HuangY.H. ChenM. SuJ. ZouY. BardeesyN. Iacobuzio-DonahueC.A. MassaguéJ. TGF-β Tumor Suppression through a Lethal EMT.Cell201616451015103010.1016/j.cell.2016.01.00926898331
    [Google Scholar]
  33. YangT. XiongY. ZengY. WangY. ZengJ. LiuJ. XuS. LiL.S. Current status of immunotherapy for non-small cell lung cancer.Front. Pharmacol.20221398946110.3389/fphar.2022.98946136313314
    [Google Scholar]
  34. DasJ.M. DasJ.M. Immunotherapy.Neuro-oncology explained through multiple choice questions.Springer International PublishingCham202310911510.1007/978‑3‑031‑13253‑7_10
    [Google Scholar]
  35. SilvaA.P. CoelhoP.V. AnazettiM. SimioniP.U. Targeted therapies for the treatment of non-small-cell lung cancer: Monoclonal antibodies and biological inhibitors.Hum Vaccin Immunother2017134843853
    [Google Scholar]
  36. TanAC TanDSW Targeted therapies for lung cancer patients with oncogenic driver molecular alterations.J Clin Oncol2022Feb 20; 40(6): 611-625.10.1200/JCO.21.01626 34985916
    [Google Scholar]
  37. ZhongS. CuiY. LiuQ. ChenS. CAR-T cell therapy for lung cancer: A promising but challenging future.J. Thorac. Dis.20201284516452110.21037/jtd.2020.03.11832944366
    [Google Scholar]
  38. BinnewiesM Understanding the tumor immune microenvironment (TIME) for effective therapy.Nat Med201824541550
    [Google Scholar]
  39. GodfreyD.I. Le NoursJ. AndrewsD.M. UldrichA.P. RossjohnJ. UnconventionalT. Unconventional T cell targets for cancer immunotherapy.Immunity201848345347310.1016/j.immuni.2018.03.00929562195
    [Google Scholar]
  40. BruchardM. GhiringhelliF. Deciphering the roles of innate lymphoid cells in cancer.Front. Immunol.20191065610.3389/fimmu.2019.0065631024531
    [Google Scholar]
  41. LekoV. RosenbergS.A. Identifying and targeting human tumor antigens for T cell-based immunotherapy of solid tumors.Cancer Cell202038445447210.1016/j.ccell.2020.07.01332822573
    [Google Scholar]
  42. GouQ PD-L1 degradation pathway and immunotherapy for cancer.Cell Death Dis202011955
    [Google Scholar]
  43. IwaiYoshiko Cancer immunotherapies targeting the PD-1 signaling pathway.J Biomed Sci201724126
    [Google Scholar]
  44. Zhou C, Liu Q, Xiang Y, Gou X, Li W. Role of the tumor immune microenvironment in tumor immunotherapy (Review). Oncol Lett 2022; 23(2): 53. Available from: https://www.spandidos-publications.com/10.3892/ol.2021.13171
  45. ZhaiY. MoosaviR. ChenM. Immune checkpoints, a novel class of therapeutic targets for autoimmune diseases.Front. Immunol.20211264569910.3389/fimmu.2021.64569933968036
    [Google Scholar]
  46. TangT. HuangX. ZhangG. HongZ. BaiX. LiangT. Advantages of targeting the tumor immune microenvironment over blocking immune checkpoint in cancer immunotherapy.Signal Transduct. Target. Ther.2021617210.1038/s41392‑020‑00449‑433608497
    [Google Scholar]
  47. MalhotraJ. JabbourS.K. AisnerJ. Current state of immunotherapy for non-small cell lung cancer.Transl. Lung Cancer Res.20076219621110.21037/tlcr.2017.03.0128529902
    [Google Scholar]
  48. AdhikaryS. Current technologies and future perspectives in immunotherapy towards a clinical oncology approachBiomedicines2024121217
    [Google Scholar]
  49. WuerdemannN LAG-3, TIM-3 and VISTA expression on tumor-infiltrating lymphocytes in oropharyngeal squamous cell carcinoma—potential biomarkers for targeted therapy conceptsInt. J. Mol. Sci.2021221379
    [Google Scholar]
  50. CaiL. Targeting LAG-3, TIM-3, and TIGIT for cancer immunotherapy.J Hematol Oncol202316101
    [Google Scholar]
  51. SobhaniNavid CTLA-4 in regulatory T cells for cancer immunotherapyCancers20211361440
    [Google Scholar]
  52. ZabetiT.A. MicroRNAs as regulators of immune checkpoints in cancer immunotherapy: Targeting PD-1/PD-L1 and CTLA-4 pathways.Cancer Cell Int202424102
    [Google Scholar]
  53. SafiM. AhmedH. Al-AzabM. XiaY. ShanX. Al-radhiM. Al-danakhA. ShopitA. LiuJ. PD-1/PDL-1 inhibitors and cardiotoxicity; molecular, etiological and management outlines.J. Adv. Res.202129455410.1016/j.jare.2020.09.00633842004
    [Google Scholar]
  54. WojtukiewiczM.Z. RekM.M. KarpowiczK. GórskaM. PolityńskaB. WojtukiewiczA.M. MoniuszkoM. RadziwonP. TuckerS.C. HonnK.V. Inhibitors of immune checkpoints—PD-1, PD-L1, CTLA-4—new opportunities for cancer patients and a new challenge for internists and general practitioners.Cancer Metastasis Rev.202140394998210.1007/s10555‑021‑09976‑034236546
    [Google Scholar]
  55. JinS. SunY. LiangX. GuX. NingJ. XuY. ChenS. PanL. Emerging new therapeutic antibody derivatives for cancer treatment.Signal Transduct. Target. Ther.2022713910.1038/s41392‑021‑00868‑x35132063
    [Google Scholar]
  56. YangJ. WuZ. ZhangL. Therapeutic strategies for EGFR- mutated non-small cell lung cancer patients with osimertinib resistance.J. Hematol. Oncol.2022151173Available from: https://link.springer.com/article/ 10.1186/s13045-022-01391-4
    [Google Scholar]
  57. RajdevK. SiddiquiA.H. IbrahimU. An unusually aggressive large cell carcinoma of the lung: undiagnosed until autopsy2018102Available from: https://www.cureus.com/articles/10689 -an-unusually-aggressive-large-cell-carcinoma-of-the-lung-undiagnosed-until-autopsy
  58. RADH.S. MonkmanJ. WarkianiM.E. Understanding the tumor microenvironment for effective immunotherapy2021: 25Available from: https://onlinelibrary.wiley.com/doi/full/10.1002/ med.21765
  59. WangZ. KimJ. ZhangP. GalvanA.J.M. JiangY. RongL. Current therapy and development of therapeutic agents for lung cancer.Cell Insight20221210001510.1016/j.cellin.2022.10001537193130
    [Google Scholar]
  60. Okobi TJ, Uhomoibhi TO, Akahara DE, et al. Immune checkpoint inhibitors as a treatment option for bladder cancer: Current evidence. Cureus 2023. Available from: https://www.cureus.com/articles/160204-immune-checkpoint-inhibitors-as-a-treatment-option- for-bladder-cancer-current-evidence
  61. MaffuidK. Decoding the complexity of immune–cancer cell interactions: Empowering the future of cancer immunotherapyCancers202315164188
    [Google Scholar]
  62. GuptaS.L. Immunotherapy: An alternative promising therapeutic approach against cancersMol Biol Rep20224999039913
    [Google Scholar]
  63. StewartJ.M. KeselowskyB.G. Combinatorial drug delivery approaches for immunomodulation.Adv. Drug Deliv. Rev.201711416117410.1016/j.addr.2017.05.01328532690
    [Google Scholar]
  64. QuJ. Mechanism and potential predictive biomarkers of immune checkpoint inhibitors in NSCLCB&P2020127109996
    [Google Scholar]
  65. PopperH.H. Progression and metastasis of lung cancerCancer Metastasis Rev2016357591
    [Google Scholar]
  66. PunekarS.R. ShumE. GrelloC.M. LauS.C. VelchetiV. Immunotherapy in non-small cell lung cancer: Past, present, and future directions.Front. Oncol.20221287759410.3389/fonc.2022.87759435992832
    [Google Scholar]
  67. HaibeY. KreidiehM. El HajjH. KhalifehI. MukherjiD. TemrazS. ShamseddineA. Resistance mechanisms to anti-angiogenic therapies in cancer.Front. Oncol.20201022110.3389/fonc.2020.0022132175278
    [Google Scholar]
  68. LiMSC Developments in targeted therapy & immunotherapy—how non-small cell lung cancer management will change in the next decade: A narrative reviewAnn Transl Med202311358
    [Google Scholar]
  69. LiS. Emerging targeted therapies in advanced non-small-cell lung cancer.Cancers202315112899
    [Google Scholar]
  70. GiulianoS. PagèsG. Mechanisms of resistance to anti-angiogenesis therapies.Biochimie20139561110111910.1016/j.biochi.2013.03.00223507428
    [Google Scholar]
  71. JavedA.M. Cancer combination therapies by angiogenesis inhibitors; a comprehensive review.Cell Commun Signal20222049
    [Google Scholar]
  72. TzengHong-Tai Tumor vasculature as an emerging pharmacological target to promote anti-tumor immunityInt. J. Mol. Sci.20232454422
    [Google Scholar]
  73. MumtazH Exploring alternative approaches to precision medicine through genomics and artificial intelligence - a systematic reviewFront Med (Lausanne)2023101227168
    [Google Scholar]
  74. YuS HLA loss of heterozygosity-mediated discordant responses to immune checkpoint blockade in squamous cell lung cancer with renal metastasisImmunotherapy202013195200
    [Google Scholar]
  75. AbbasianM.H. ArdekaniA.M. SobhaniN. RoudiR. The role of genomics and proteomics in lung cancer early detection and treatment.Cancers20221420514410.3390/cancers1420514436291929
    [Google Scholar]
  76. PandeyP. KhanF. QariH.A. UpadhyayT.K. AlkhateebA.F. OvesM. Revolutionization in cancer therapeutics via targeting major immune checkpoints PD-1, PD-L1 and CTLA-4.Pharmaceuticals202215333510.3390/ph1503033535337133
    [Google Scholar]
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