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2000
Volume 24, Issue 20
  • ISSN: 1871-5206
  • E-ISSN: 1875-5992

Abstract

Interleukin-15 (IL-15) was identified in 1994 as a T-cell growth factor with the capability to mimic the functions of IL-2. IL-15 engages with the IL-15Rα subunit expressed on the surface of antigen-presenting cells (APCs) and, through a trans-presentation mechanism, activates the IL-2/IL-15Rβγ complex receptor on the surface of natural killer (NK) cells and CD8+ T cells. This interaction initiates a cascade of downstream signaling pathways, playing a pivotal role in the activation, proliferation, and anti-apoptotic processes in NK cells, CD8+ T cells, and B cells. It provides a substantial theoretical foundation and potential therapeutic targets for tumor immunotherapy. Whether through active or passive immunotherapeutic strategies, IL-15 has emerged as a critical molecule for stimulating anti-tumor cell proliferation.

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References

  1. LiuZ. HanC. FuY.X. Targeting innate sensing in the tumor microenvironment to improve immunotherapy.Cell. Mol. Immunol.2020171132610.1038/s41423‑019‑0341‑y 31844141
     [Google Scholar]
  2. TakatsuK. NakajimaH. IL-5 and eosinophilia.Curr. Opin. Immunol.200820328829410.1016/j.coi.2008.04.001 18511250
     [Google Scholar]
  3. WengN.P. LiuK. CatalfamoM. LiY. HenkartP.A. IL-15 is a growth factor and an activator of CD8 memory T cells.Ann. N. Y. Acad. Sci.20029751465610.1111/j.1749‑6632.2002.tb05940.x 12538153
     [Google Scholar]
  4. GiriJ.G. AndersonD.M. KumakiS. ParkL.S. GrabsteinK.H. CosmanD. IL-15, a novel T cell growth factor that shares activities and receptor components with IL-2.J. Leukoc. Biol.199557576376610.1002/jlb.57.5.763 7759955
     [Google Scholar]
  5. FehnigerT.A. Mystery solved: IL-15.J. Immunol.2019202113125312610.4049/jimmunol.1900419 31109944
     [Google Scholar]
  6. YangY. LundqvistA. Immunomodulatory effects of IL-2 and IL-15; implications for cancer immunotherapy.Cancers (Basel)20201212358610.3390/cancers12123586 33266177
     [Google Scholar]
  7. BilottaM.T. AntignaniA. FitzgeraldD.J. Managing the TME to improve the efficacy of cancer therapy.Front. Immunol.20221395499210.3389/fimmu.2022.954992 36341428
     [Google Scholar]
  8. BeckerJ.C. AndersenM.H. SchramaD. thor StratenP. Immune-suppressive properties of the tumor microenvironment.Cancer Immunol. Immunother.20136271137114810.1007/s00262‑013‑1434‑6 23666510
     [Google Scholar]
  9. HanahanD. CoussensL.M. Accessories to the crime: functions of cells recruited to the tumor microenvironment.Cancer Cell201221330932210.1016/j.ccr.2012.02.022 22439926
     [Google Scholar]
  10. ManninoM.H. ZhuZ. XiaoH. BaiQ. WakefieldM.R. FangY. The paradoxical role of IL-10 in immunity and cancer.Cancer Lett.2015367210310710.1016/j.canlet.2015.07.009 26188281
     [Google Scholar]
  11. LarsonC. OronskyB. CarterC.A. OronskyA. KnoxS.J. SherD. ReidT.R. TGF-beta: a master immune regulator.Expert Opin. Ther. Targets202024542743810.1080/14728222.2020.1744568 32228232
     [Google Scholar]
  12. VaupelP. MulthoffG. Accomplices of the hypoxic tumor microenvironment compromising antitumor immunity: Adenosine, lactate, acidosis, vascular endothelial growth factor, potassium ions, and phosphatidylserine.Front. Immunol.20178188710.3389/fimmu.2017.01887 29312351
     [Google Scholar]
  13. MaddenM.Z. RathmellJ.C. The complex integration of T-cell metabolism and immunotherapy.Cancer Discov.20211171636164310.1158/2159‑8290.CD‑20‑0569 33795235
     [Google Scholar]
  14. YanJ. SmythM.J. TengM.W.L. Interleukin (IL)-12 and IL-23 and their conflicting roles in cancer.Cold Spring Harb. Perspect. Biol.2018107a02853010.1101/cshperspect.a028530 28716888
     [Google Scholar]
  15. TakakiS. KanazawaH. ShiibaM. TakatsuK. A critical cytoplasmic domain of the interleukin-5 (IL-5) receptor alpha chain and its function in IL-5-mediated growth signal transduction.Mol. Cell. Biol.199414117404741310.1128/MCB.14.11.7404 7935454
     [Google Scholar]
  16. MlecnikB. BindeaG. AngellH.K. SassoM.S. ObenaufA.C. FredriksenT. LafontaineL. BilocqA.M. KirilovskyA. TosoliniM. WaldnerM. BergerA. FridmanW.H. RafiiA. Valge-ArcherV. PagèsF. SpeicherM.R. GalonJ. Functional network pipeline reveals genetic determinants associated with in situ lymphocyte proliferation and survival of cancer patients.Sci. Transl. Med.20146228228ra3710.1126/scitranslmed.3007240 24648340
     [Google Scholar]
  17. ‘Mac’ Cheever, M.A. Twelve immunotherapy drugs that could cure cancers.Immunol. Rev.2008222135736810.1111/j.1600‑065X.2008.00604.x 18364014
     [Google Scholar]
  18. GiriJ.G. KumakiS. AhdiehM. FriendD.J. LoomisA. ShanebeckK. DuBoseR. CosmanD. ParkL.S. AndersonD.M. Identification and cloning of a novel IL-15 binding protein that is structurally related to the alpha chain of the IL-2 receptor.EMBO J.199514153654366310.1002/j.1460‑2075.1995.tb00035.x 7641685
     [Google Scholar]
  19. BadoualC. BouchaudG. AgueznayN.E.H. MortierE. HansS. GeyA. FernaniF. PeyrardS. -PuigP.L. BrunevalP. SastreX. PletA. Garrigue-AntarL. Quintin-ColonnaF. FridmanW.H. BrasnuD. JacquesY. TartourE. The soluble alpha chain of interleukin-15 receptor: a proinflammatory molecule associated with tumor progression in head and neck cancer.Cancer Res.200868103907391410.1158/0008‑5472.CAN‑07‑6842 18483276
     [Google Scholar]
  20. ZhangN. BevanM.J. CD8(+) T cells: foot soldiers of the immune system.Immunity201135216116810.1016/j.immuni.2011.07.010 21867926
     [Google Scholar]
  21. ReiserJ. BanerjeeA. Effector, memory, and dysfunctional CD8 + T cell fates in the antitumor immune response.J. Immunol. Res.2016201611410.1155/2016/8941260 27314056
     [Google Scholar]
  22. KlebanoffC.A. GattinoniL. PalmerD.C. MuranskiP. JiY. HinrichsC.S. BormanZ.A. KerkarS.P. ScottC.D. FinkelsteinS.E. RosenbergS.A. RestifoN.P. Determinants of successful CD8+ T-cell adoptive immunotherapy for large established tumors in mice.Clin. Cancer Res.201117165343535210.1158/1078‑0432.CCR‑11‑0503 21737507
     [Google Scholar]
  23. GaoS. LiangX. WangH. BaoB. ZhangK. ZhuY. ShaoQ. Stem cell-like memory T cells: A perspective from the dark side.Cell. Immunol.202136110427310.1016/j.cellimm.2020.104273 33422699
     [Google Scholar]
  24. GermainR.N. T-cell development and the CD4–CD8 lineage decision.Nat. Rev. Immunol.20022530932210.1038/nri798 12033737
     [Google Scholar]
  25. LuC. LiuY. AliN.M. ZhangB. CuiX. The role of innate immune cells in the tumor microenvironment and research progress in anti-tumor therapy.Front. Immunol.202313103926010.3389/fimmu.2022.1039260 36741415
     [Google Scholar]
  26. KucuksezerU.C. Aktas CetinE. EsenF. TahraliI. AkdenizN. GelmezM.Y. DenizG. The role of natural killer cells in autoimmune diseases.Front. Immunol.20211262230610.3389/fimmu.2021.622306 33717125
     [Google Scholar]
  27. NolzJ.C. RicherM.J. Control of memory CD8+ T cell longevity and effector functions by IL-15.Mol. Immunol.202011718018810.1016/j.molimm.2019.11.011 31816491
     [Google Scholar]
  28. BlankC.U. HainingW.N. HeldW. HoganP.G. KalliesA. LugliE. LynnR.C. PhilipM. RaoA. RestifoN.P. SchietingerA. SchumacherT.N. SchwartzbergP.L. SharpeA.H. SpeiserD.E. WherryE.J. YoungbloodB.A. ZehnD. Defining ‘T cell exhaustion’.Nat. Rev. Immunol.2019191166567410.1038/s41577‑019‑0221‑9 31570879
     [Google Scholar]
  29. LeeJ. LeeK. BaeH. LeeK. LeeS. MaJ. JoK. KimI. JeeB. KangM. ImS.J. IL-15 promotes self-renewal of progenitor exhausted CD8 T cells during persistent antigenic stimulation.Front. Immunol.202314111709210.3389/fimmu.2023.1117092 37409128
     [Google Scholar]
  30. O’SullivanD. van der WindtG.J.W. HuangS.C.C. CurtisJ.D. ChangC.H. BuckM.D. QiuJ. SmithA.M. LamW.Y. DiPlatoL.M. HsuF.F. BirnbaumM.J. PearceE.J. PearceE.L. Memory CD8+ T cells use cell-intrinsic lipolysis to support the metabolic programming necessary for development.Immunity201849237537610.1016/j.immuni.2018.07.018 30134202
     [Google Scholar]
  31. KurtulusS. TripathiP. Moreno-FernandezM.E. ShollA. KatzJ.D. GrimesH.L. HildemanD.A. Bcl-2 allows effector and memory CD8+ T cells to tolerate higher expression of Bim.J. Immunol.2011186105729573710.4049/jimmunol.1100102 21451108
     [Google Scholar]
  32. WaldmannT.A. MiljkovicM.D. ConlonK.C. Interleukin-15 (dys)regulation of lymphoid homeostasis: Implications for therapy of autoimmunity and cancer.J. Exp. Med.20202171e2019106210.1084/jem.20191062 31821442
     [Google Scholar]
  33. GoldrathA.W. SivakumarP.V. GlaccumM. KennedyM.K. BevanM.J. BenoistC. MathisD. ButzE.A. Cytokine requirements for acute and Basal homeostatic proliferation of naive and memory CD8+ T cells.J. Exp. Med.2002195121515152210.1084/jem.20020033 12070279
     [Google Scholar]
  34. SchlunsK.S. WilliamsK. MaA. ZhengX.X. LefrançoisL. Cutting edge: requirement for IL-15 in the generation of primary and memory antigen-specific CD8 T cells.J. Immunol.2002168104827483110.4049/jimmunol.168.10.4827 11994430
     [Google Scholar]
  35. TanJ.T. ErnstB. KieperW.C. LeRoyE. SprentJ. SurhC.D. Interleukin (IL)-15 and IL-7 jointly regulate homeostatic proliferation of memory phenotype CD8+ cells but are not required for memory phenotype CD4+ cells.J. Exp. Med.2002195121523153210.1084/jem.20020066 12070280
     [Google Scholar]
  36. KurzE. HirschC.A. DaltonT. ShadaloeyS.A. Khodadadi-JamayranA. MillerG. PareekS. RajaeiH. MohindrooC. BaydoganS. Ngo-HuangA. ParkerN. KatzM.H.G. PetzelM. VucicE. McAllisterF. SchadlerK. WinogradR. Bar-SagiD. Exercise-induced engagement of the IL-15/IL-15Rα axis promotes anti-tumor immunity in pancreatic cancer.Cancer Cell2022407720737.e510.1016/j.ccell.2022.05.006 35660135
     [Google Scholar]
  37. AliA.K. NandagopalN. LeeS.H. IL-15–PI3K–AKT–mTOR: A critical pathway in the life journey of natural killer cells.Front. Immunol.2015635510.3389/fimmu.2015.00355 26257729
     [Google Scholar]
  38. CheukS. SchlumsH. Gallais SérézalI. MartiniE. ChiangS.C. MarquardtN. GibbsA. DetlofssonE. IntroiniA. ForkelM. HöögC. TjernlundA. MichaëlssonJ. FolkersenL. MjösbergJ. BlomqvistL. EhrströmM. StåhleM. BrycesonY.T. EidsmoL. CD49a expression defines tissue-resident CD8+ T cells poised for cytotoxic function in human skin.Immunity201746228730010.1016/j.immuni.2017.01.009 28214226
     [Google Scholar]
  39. ZhouX. YuJ. ChengX. ZhaoB. ManyamG.C. ZhangL. SchlunsK. LiP. WangJ. SunS.C. The deubiquitinase Otub1 controls the activation of CD8+ T cells and NK cells by regulating IL-15-mediated priming.Nat. Immunol.201920787988910.1038/s41590‑019‑0405‑2 31182807
     [Google Scholar]
  40. RauletD.H. VanceR.E. Self-tolerance of natural killer cells.Nat. Rev. Immunol.20066752053110.1038/nri1863 16799471
     [Google Scholar]
  41. SoelistyoningsihD. SusiantiH. KalimH. HandonoK. The phenotype of CD3–CD56bright and CD3–CD56dim natural killer cells in systemic lupus erythematosus patients and its relation to disease activity.Reumatologia202260425826510.5114/reum.2022.119042 36186836
     [Google Scholar]
  42. PoznanskiS.M. AshkarA.A. Shining light on the significance of NK cell CD56 brightness.Cell. Mol. Immunol.201815121071107310.1038/s41423‑018‑0163‑3 30275534
     [Google Scholar]
  43. MichelT. PoliA. CuapioA. BriquemontB. IserentantG. OllertM. ZimmerJ. Human CD56 bright NK cells: An update.J. Immunol.201619672923293110.4049/jimmunol.1502570 26994304
     [Google Scholar]
  44. KochJ. SteinleA. WatzlC. MandelboimO. Activating natural cytotoxicity receptors of natural killer cells in cancer and infection.Trends Immunol.201334418219110.1016/j.it.2013.01.003 23414611
     [Google Scholar]
  45. TerrénI. OrrantiaA. VitalléJ. Astarloa-PandoG. ZenarruzabeitiaO. BorregoF. Modulating NK cell metabolism for cancer immunotherapy.Semin. Hematol.202057421322410.1053/j.seminhematol.2020.10.003 33256914
     [Google Scholar]
  46. CorreiaA.L. GuimaraesJ.C. Auf der MaurP. De SilvaD. TrefnyM.P. OkamotoR. BrunoS. SchmidtA. MertzK. VolkmannK. TerraccianoL. ZippeliusA. VetterM. KurzederC. WeberW.P. Bentires-AljM. Hepatic stellate cells suppress NK cell-sustained breast cancer dormancy.Nature2021594786456657110.1038/s41586‑021‑03614‑z 34079127
     [Google Scholar]
  47. CastilloE.F. SchlunsK.S. Regulating the immune system via IL-15 transpresentation.Cytokine201259347949010.1016/j.cyto.2012.06.017 22795955
     [Google Scholar]
  48. BalsamoM. ScordamagliaF. PietraG. ManziniC. CantoniC. BoitanoM. QueiroloP. VermiW. FacchettiF. MorettaA. MorettaL. MingariM.C. VitaleM. Melanoma-associated fibroblasts modulate NK cell phenotype and antitumor cytotoxicity.Proc. Natl. Acad. Sci. USA200910649208472085210.1073/pnas.0906481106 19934056
     [Google Scholar]
  49. MaS. CaligiuriM.A. YuJ. Harnessing IL-15 signaling to potentiate NK cell-mediated cancer immunotherapy.Trends Immunol.2022431083384710.1016/j.it.2022.08.004 36058806
     [Google Scholar]
  50. DeanI. LeeC.Y.C. TuongZ.K. LiZ. TibbittC.A. WillisC. GaspalF. KennedyB.C. Matei-RascuV. FiancetteR. NordenvallC. LindforssU. BakerS.M. StockmannC. SexlV. HammondS.A. DovediS.J. MjösbergJ. HepworthM.R. CarlessoG. ClatworthyM.R. WithersD.R. Rapid functional impairment of natural killer cells following tumor entry limits anti-tumor immunity.Nat. Commun.202415168310.1038/s41467‑024‑44789‑z 38267402
     [Google Scholar]
  51. MishraH.K. DixonK.J. PoreN. FelicesM. MillerJ.S. WalcheckB. Activation of ADAM17 by IL-15 limits human NK cell proliferation.Front. Immunol.20211271162110.3389/fimmu.2021.711621 34367174
     [Google Scholar]
  52. WatkinsonF. NayarS.K. RaniA. SakellariouC.A. ElhageO. PapaevangelouE. DasguptaP. GalustianC. IL-15 upregulates telomerase expression and potently increases proliferative capacity of NK, NKT-like, and CD8 T cells.Front. Immunol.20211159462010.3389/fimmu.2020.594620 33537030
     [Google Scholar]
  53. GhoshA.K. SinhaD. BiswasR. BiswasT. IL-15 stimulates NKG2D while promoting IgM expression of B-1a cells.Cytokine201795435010.1016/j.cyto.2017.02.014 28235675
     [Google Scholar]
  54. ZhangC. ZhangJ. NiuJ. ZhangJ. TianZ. Interleukin-15 improves cytotoxicity of natural killer cells via up-regulating NKG2D and cytotoxic effector molecule expression as well as STAT1 and ERK1/2 phosphorylation.Cytokine200842112813610.1016/j.cyto.2008.01.003 18280748
     [Google Scholar]
  55. KhamenehH.J. FontaN. ZenobiA. NiogretC. VenturaP. GuerraC. KweeI. RinaldiA. PecoraroM. GeigerR. CavalliA. BertoniF. VivierE. TrumppA. GuardaG. Myc controls NK cell development, IL-15-driven expansion, and translational machinery.Life Sci. Alliance202367e20230206910.26508/lsa.202302069 37105715
     [Google Scholar]
  56. WangX. ZhaoX.Y. Transcription factors associated with IL-15 cytokine signaling during NK cell development.Front. Immunol.20211261078910.3389/fimmu.2021.610789 33815365
     [Google Scholar]
  57. CarsonW.E. FehnigerT.A. HaldarS. EckhertK. LindemannM.J. LaiC.F. CroceC.M. BaumannH. CaligiuriM.A. A potential role for interleukin-15 in the regulation of human natural killer cell survival.J. Clin. Invest.199799593794310.1172/JCI119258 9062351
     [Google Scholar]
  58. HuntingtonN.D. PuthalakathH. GunnP. NaikE. MichalakE.M. SmythM.J. TabariasH. Degli-EspostiM.A. DewsonG. WillisS.N. MotoyamaN. HuangD.C.S. NuttS.L. TarlintonD.M. StrasserA. Interleukin 15–mediated survival of natural killer cells is determined by interactions among Bim, Noxa and Mcl-1.Nat. Immunol.20078885686310.1038/ni1487 17618288
     [Google Scholar]
  59. KokaR. BurkettP.R. ChienM. ChaiS. ChanF. LodolceJ.P. BooneD.L. MaA. Interleukin (IL)-15R[alpha]-deficient natural killer cells survive in normal but not IL-15R[alpha]-deficient mice.J. Exp. Med.2003197897798410.1084/jem.20021836 12695489
     [Google Scholar]
  60. OberoiP. KamenjarinK. Villena OssaJ.F. UherekB. BönigH. WelsW.S. Directed differentiation of mobilized hematopoietic stem and progenitor cells into functional NK cells with enhanced antitumor activity.Cells20209481110.3390/cells9040811 32230942
     [Google Scholar]
  61. WangY. ZhangY. YiP. DongW. NalinA.P. ZhangJ. ZhuZ. ChenL. BensonD.M. Mundy-BosseB.L. FreudA.G. CaligiuriM.A. YuJ. The IL-15–AKT–XBP1s signaling pathway contributes to effector functions and survival in human NK cells.Nat. Immunol.2019201101710.1038/s41590‑018‑0265‑1 30538328
     [Google Scholar]
  62. MaS. HanJ. LiZ. XiaoS. ZhangJ. YanJ. TangT. BarrT. KraftA.S. CaligiuriM.A. YuJ. An XBP1s–PIM-2 positive feedback loop controls IL-15–mediated survival of natural killer cells.Sci. Immunol.2023881eabn799310.1126/sciimmunol.abn7993 36897958
     [Google Scholar]
  63. RoyK. ChakrabortyM. KumarA. MannaA.K. RoyN.S. The NFκB signaling system in the generation of B-cell subsets: from germinal center B cells to memory B cells and plasma cells.Front. Immunol.202314118559710.3389/fimmu.2023.1185597 38169968
     [Google Scholar]
  64. CargillT. CulverE.L. The role of B cells and B cell therapies in immune-mediated liver diseases.Front. Immunol.20211266119610.3389/fimmu.2021.661196 33936097
     [Google Scholar]
  65. WangY. LiuJ. BurrowsP.D. WangJ.Y. B cell development and maturation.Adv. Exp. Med. Biol.2020125412210.1007/978‑981‑15‑3532‑1_1 32323265
     [Google Scholar]
  66. YoshimotoM. The ontogeny of murine B-1a cells.Int. J. Hematol.2020111562262710.1007/s12185‑019‑02787‑8 31802412
     [Google Scholar]
  67. SabatinoJ.J.Jr PröbstelA.K. ZamvilS.S. B cells in autoimmune and neurodegenerative central nervous system diseases.Nat. Rev. Neurosci.2019201272874510.1038/s41583‑019‑0233‑2 31712781
     [Google Scholar]
  68. AndersonN.M. SimonM.C. The tumor microenvironment.Curr. Biol.20203016R921R92510.1016/j.cub.2020.06.081 32810447
     [Google Scholar]
  69. ChandnaniN. GuptaI. MandalA. SarkarK. Participation of B cell in immunotherapy of cancer.Pathol. Res. Pract.202425515516910.1016/j.prp.2024.155169 38330617
     [Google Scholar]
  70. RastogiI. JeonD. MosemanJ.E. MuralidharA. PotluriH.K. McNeelD.G. Role of B cells as antigen presenting cells.Front. Immunol.20221395493610.3389/fimmu.2022.954936 36159874
     [Google Scholar]
  71. LaumontC.M. NelsonB.H. B cells in the tumor microenvironment: Multi-faceted organizers, regulators, and effectors of anti-tumor immunity.Cancer Cell202341346648910.1016/j.ccell.2023.02.017 36917951
     [Google Scholar]
  72. ArmitageR.J. MacduffB.M. EisenmanJ. PaxtonR. GrabsteinK.H. IL-15 has stimulatory activity for the induction of B cell proliferation and differentiation.J. Immunol.1995154248349010.4049/jimmunol.154.2.483 7814861
     [Google Scholar]
  73. Kanti GhoshA. SinhaD. MukherjeeS. BiswasR. BiswasT. IL-15 temporally reorients IL-10 biased B-1a cells toward IL-12 expression.Cell. Mol. Immunol.201613222923910.1038/cmi.2015.08 25748019
     [Google Scholar]
  74. GillN. PaltserG. AshkarA.A. Interleukin-15 expression affects homeostasis and function of B cells through NK cell-derived interferon-γ.Cell. Immunol.20092581596410.1016/j.cellimm.2009.03.010 19361783
     [Google Scholar]
  75. WaldmannT. DuboisS. TagayaY. Contrasting roles of IL-2 and IL-15 in the life and death of lymphocytes: implications for immunotherapy.Immunity200114210511010.1016/S1074‑7613(09)00091‑0 11239443
     [Google Scholar]
  76. NagyÉ. MocsárG. SebestyénV. VolkóJ. PappF. TóthK. DamjanovichS. PanyiG. WaldmannT.A. BodnárA. VámosiG. Membrane Potential Distinctly Modulates Mobility and Signaling of IL-2 and IL-15 Receptors in T Cells.Biophys. J.2018114102473248210.1016/j.bpj.2018.04.038 29754714
     [Google Scholar]
  77. HiltonL.R. RätsepM.T. VandenBroekM.M. JafriS. LavertyK.J. MitchellM. TheilmannA.L. SmartJ.A. HawkeL.G. MooreS.D. RenaudS.J. SoaresM.J. MorrellN.W. OrmistonM.L. Impaired interleukin-15 signaling via BMPR2 loss drives natural killer cell deficiency and pulmonary hypertension.Hypertension202279112493250410.1161/HYPERTENSIONAHA.122.19178 36043416
     [Google Scholar]
  78. ChoiY.J. LeeH. KimJ.H. KimS.Y. KohJ.Y. SaM. ParkS.H. ShinE.C. CD5 suppresses IL-15–induced proliferation of human memory CD8+ T cells by inhibiting mTOR pathways.J. Immunol.202220961108111710.4049/jimmunol.2100854 36002232
     [Google Scholar]
  79. MaS. TangT. WuX. MansourA.G. LuT. ZhangJ. WangL.S. CaligiuriM.A. YuJ. PDGF-D−PDGFRβ signaling enhances IL-15–mediated human natural killer cell survival.Proc. Natl. Acad. Sci. USA20221193e211413411910.1073/pnas.2114134119 35027451
     [Google Scholar]
  80. RaeberM.E. SahinD. BoymanO. Interleukin-2–based therapies in cancer.Sci. Transl. Med.202214670eabo540910.1126/scitranslmed.abo5409 36350987
     [Google Scholar]
  81. ReardonS. How to supercharge cancer-fighting cells: give them stem-cell skills.Nature2024628800848610.1038/d41586‑024‑01043‑2 38600202
     [Google Scholar]
  82. ChapovalA.I. FullerJ.A. KremlevS.G. KamdarS.J. EvansR. Combination chemotherapy and IL-15 administration induce permanent tumor regression in a mouse lung tumor model: NK and T cell-mediated effects antagonized by B cells.J. Immunol.1998161126977698410.4049/jimmunol.161.12.6977 9862733
     [Google Scholar]
  83. Van BelleT. GrootenJ. IL-15 and IL-15Ralpha in CD4+T cell immunity.Arch. Immunol. Ther. Exp. (Warsz.)2005532115126 15928580
     [Google Scholar]
  84. BergamaschiC. PanditH. NagyB.A. StellasD. JensenS.M. BearJ. CamM. ValentinA. FoxB.A. FelberB.K. PavlakisG.N. Heterodimeric IL-15 delays tumor growth and promotes intratumoral CTL and dendritic cell accumulation by a cytokine network involving XCL1, IFN-γ, CXCL9 and CXCL10.J. Immunother. Cancer202081e00059910.1136/jitc‑2020‑000599 32461349
     [Google Scholar]
  85. RubinsteinM.P. KovarM. PurtonJ.F. ChoJ.H. BoymanO. SurhC.D. SprentJ. Converting IL-15 to a superagonist by binding to soluble IL-15Rα.Proc. Natl. Acad. Sci. USA2006103249166917110.1073/pnas.0600240103 16757567
     [Google Scholar]
  86. ZhuX. MarcusW.D. XuW. LeeH. HanK. EganJ.O. YovandichJ.L. RhodeP.R. WongH.C. Novel human interleukin-15 agonists.J. Immunol.200918363598360710.4049/jimmunol.0901244 19710453
     [Google Scholar]
  87. WaldmannT.A. DuboisS. MiljkovicM.D. ConlonK.C. IL-15 in the combination immunotherapy of cancer.Front. Immunol.20201186810.3389/fimmu.2020.00868 32508818
     [Google Scholar]
  88. ShenJ. ZouZ. GuoJ. CaiY. XueD. LiangY. WangW. PengH. FuY.X. An engineered concealed IL-15-R elicits tumor-specific CD8+T cell responses through PD-1-cis delivery.J. Exp. Med.202221912e2022074510.1084/jem.20220745 36165896
     [Google Scholar]
  89. HirayamaA.V. ChouC.K. MiyazakiT. SteinmetzR.N. DiH.A. FraessleS.P. GauthierJ. FiorenzaS. HawkinsR.M. OverwijkW.W. RiddellS.R. MarcondesM.Q. TurtleC.J. A novel polymer-conjugated human IL-15 improves efficacy of CD19-targeted CAR T-cell immunotherapy.Blood Adv.20237112479249310.1182/bloodadvances.2022008697 36332004
     [Google Scholar]
  90. MujibS. JonesR.B. LoC. AidarusN. ClaytonK. SakhdariA. BenkoE. KovacsC. OstrowskiM.A. Antigen-independent induction of Tim-3 expression on human T cells by the common γ-chain cytokines IL-2, IL-7, IL-15, and IL-21 is associated with proliferation and is dependent on the phosphoinositide 3-kinase pathway.J. Immunol.201218883745375610.4049/jimmunol.1102609 22422881
     [Google Scholar]
  91. ConlonK.C. LugliE. WellesH.C. RosenbergS.A. FojoA.T. MorrisJ.C. FleisherT.A. DuboisS.P. PereraL.P. StewartD.M. GoldmanC.K. BryantB.R. DeckerJ.M. ChenJ. WorthyT.Y.A. FiggW.D.Sr PeerC.J. SnellerM.C. LaneH.C. YovandichJ.L. CreekmoreS.P. RoedererM. WaldmannT.A. Redistribution, hyperproliferation, activation of natural killer cells and CD8 T cells, and cytokine production during first-in-human clinical trial of recombinant human interleukin-15 in patients with cancer.J. Clin. Oncol.2015331748210.1200/JCO.2014.57.3329 25403209
     [Google Scholar]
  92. RomeeR. CooleyS. Berrien-ElliottM.M. WesterveltP. VernerisM.R. WagnerJ.E. WeisdorfD.J. BlazarB.R. UstunC. DeForT.E. VivekS. PeckL. DiPersioJ.F. CashenA.F. KylloR. MusiekA. SchafferA. AnadkatM.J. RosmanI. MillerD. EganJ.O. JengE.K. RockA. WongH.C. FehnigerT.A. MillerJ.S. First-in-human phase 1 clinical study of the IL-15 superagonist complex ALT-803 to treat relapse after transplantation.Blood2018131232515252710.1182/blood‑2017‑12‑823757 29463563
     [Google Scholar]
  93. LiuR.B. EngelsB. SchreiberK. CiszewskiC. SchietingerA. SchreiberH. JabriB. IL-15 in tumor microenvironment causes rejection of large established tumors by T cells in a noncognate T cell receptor-dependent manner.Proc. Natl. Acad. Sci. USA2013110208158816310.1073/pnas.1301022110 23637340
     [Google Scholar]
  94. Di MatteoS. MunariE. FioreP.F. SantopoloS. SampaoliC. PelosiA. ChouaibS. TuminoN. VaccaP. MariottiF.R. EbertS. MachwirthM. HaasD. PezzulloM. PietraG. GrottoliM. BuartS. MortierE. MaggiE. MorettaL. CaruanaI. AzzaroneB. The roles of different forms of IL-15 in human melanoma progression.Front. Immunol.202314118366810.3389/fimmu.2023.1183668 37334356
     [Google Scholar]
  95. FehnigerT.A. CaligiuriM.A. Interleukin 15: biology and relevance to human disease.Blood2001971143210.1182/blood.V97.1.14 11133738
     [Google Scholar]
  96. YuanH. MengX. GuoW. CaiP. LiW. LiQ. WangW. SunY. XuQ. GuY. Transmembrane-bound IL-15–promoted epithelial-mesenchymal transition in renal cancer cells requires the Src-dependent Akt/GSK-3β/β-catenin pathway.Neoplasia201517541042010.1016/j.neo.2015.04.002 26025664
     [Google Scholar]
  97. AzziS. GallerneC. RomeiC. Le CozV. GangemiR. KhawamK. DevocelleA. GuY. BrunoS. FerriniS. ChouaibS. EidP. AzzaroneB. Giron-MichelJ. Human renal normal, tumoral, and cancer stem cells express membrane-bound interleukin-15 isoforms displaying different functions.Neoplasia201517650951710.1016/j.neo.2015.06.002 26152359
     [Google Scholar]
  98. GuoJ. LiangY. XueD. ShenJ. CaiY. ZhuJ. FuY.X. PengH. Tumor-conditional IL-15 pro-cytokine reactivates anti-tumor immunity with limited toxicity.Cell Res.202131111190119810.1038/s41422‑021‑00543‑4 34376814
     [Google Scholar]
  99. WrangleJ.M. VelchetiV. PatelM.R. Garrett-MayerE. HillE.G. RavenelJ.G. MillerJ.S. FarhadM. AndertonK. LindseyK. Taffaro-NeskeyM. ShermanC. SurianoS. Swiderska-SynM. SionA. HarrisJ. EdwardsA.R. RytlewskiJ.A. SandersC.M. YuskoE.C. RobinsonM.D. KriegC. RedmondW.L. EganJ.O. RhodeP.R. JengE.K. RockA.D. WongH.C. RubinsteinM.P. ALT-803, an IL-15 superagonist, in combination with nivolumab in patients with metastatic non-small cell lung cancer: a non-randomised, open-label, phase 1b trial.Lancet Oncol.201819569470410.1016/S1470‑2045(18)30148‑7 29628312
     [Google Scholar]
  100. BrammerJ.E. BallenK. SokolL. QuerfeldC. NakamuraR. MishraA. McLaughlinE.M. FeithD. AzimiN. WaldmannT.A. TagayaY. LoughranT. Effective treatment with the selective cytokine inhibitor BNZ-1 reveals the cytokine dependency of T-LGL leukemia.Blood2023142151271128010.1182/blood.2022017643 37352612
     [Google Scholar]
  101. SlavuljicaI. KrmpotićA. JonjićS. Manipulation of NKG2D ligands by cytomegaloviruses: impact on innate and adaptive immune response.Front. Immunol.2011285 22566874
     [Google Scholar]
/content/journals/acamc/10.2174/0118715206321574240821112747
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Immunomodulatory Roles of IL-15 in Immune Cells and its Potential for Cancer Immunotherapy
Anti-Cancer Agents in Medicinal Chemistry (Formerly Current Medicinal Chemistry - Anti-Cancer Agents) 24, 1457 (2024); https://doi.org/10.2174/0118715206321574240821112747
/content/journals/acamc/10.2174/0118715206321574240821112747
/content/journals/acamc/10.2174/0118715206321574240821112747
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  • Article Type:     Review Article
Keyword(s): B cell; CD8+T; IL-15; natural killer; NK; Tumor

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