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2000
Volume 25, Issue 7
  • ISSN: 1871-5206
  • E-ISSN: 1875-5992

Abstract

Dysregulated lipid metabolism within the tumor microenvironment (TME) is a critical hallmark of cancer progression, with lipids serving as a major energy source for tumor cells. Beyond their role in cell membrane synthesis, lipids also provide essential substrates for biomolecule production and activate signaling pathways that regulate various cellular processes. Aberrant lipid metabolism impacts not only function but also alters the behavior of immune and stromal cells within the TME. CD36, a key lipid transporter, plays a crucial role in regulating fatty acid sensing and lipid metabolism, and its dysregulated expression has been associated with poor prognosis in several cancers. Studies have demonstrated that elevated CD 36 expression in the TME is closely linked to abnormal lipid metabolism, promoting tumor growth, migration, and metastasis. In recent years, significant progress has been made in developing CD36-targeted therapies, including small-molecule inhibitors, antibodies, and nanoparticle-based drugs, with many entering experimental or preclinical stages. This review comprehensively summarizes the latest advances in understanding the role of CD36 in the TME, focusing on its metabolic regulatory mechanisms in tumor cells, immune cells, and stromal cells. Additionally, it highlights the contribution of CD36 to immune evasion, drug resistance, and cancer stem cell maintenance while discussing several therapeutic strategies targeting CD36, including novel therapies currently in clinical trials. By exploring the therapeutic potential of CD36, this review provides critical insights for the future development of CD36-targeted cancer therapies.

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2025-01-01
2025-04-20
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References

  1. LiY. HuangX. YangG. XuK. YinY. BrecchiaG. YinJ. CD36 favours fat sensing and transport to govern lipid metabolism.Prog. Lipid Res.20228810119310.1016/j.plipres.2022.101193 36055468
    [Google Scholar]
  2. WangJ. LiY. CD36 tango in cancer: Signaling pathways and functions.Theranostics20199174893490810.7150/thno.36037 31410189
    [Google Scholar]
  3. FengW.W. ZuppeH.T. KurokawaM. The role of CD36 in cancer progression and its value as a therapeutic target.Cells20231212160510.3390/cells12121605 37371076
    [Google Scholar]
  4. LuikenJ.J.F.P. ChandaD. NabbenM. NeumannD. GlatzJ.F.C. Post-translational modifications of CD36 (SR-B2): Implications for regulation of myocellular fatty acid uptake.Biochim. Biophys. Acta Mol. Basis Dis.20161862122253225810.1016/j.bbadis.2016.09.004 27615427
    [Google Scholar]
  5. DingZ. LiuS. WangX. TheusS. DengX. FanY. ZhouS. MehtaJ.L. PCSK9 regulates expression of scavenger receptors and ox-LDL uptake in macrophages.Cardiovasc. Res.201811481145115310.1093/cvr/cvy079 29617722
    [Google Scholar]
  6. JayA.G. ChenA.N. PazM.A. HungJ.P. HamiltonJ.A. CD36 binds oxidized low density lipoprotein (LDL) in a mechanism dependent upon fatty acid binding.J. Biol. Chem.201529084590460310.1074/jbc.M114.627026 25555908
    [Google Scholar]
  7. NeubauerE.F. PooleA.Z. WeisV.M. DavyS.K. The scavenger receptor repertoire in six cnidarian species and its putative role in cnidarian-dinoflagellate symbiosis.PeerJ20164e269210.7717/peerj.2692 27896028
    [Google Scholar]
  8. NeculaiD. SchwakeM. RavichandranM. ZunkeF. CollinsR.F. PetersJ. NeculaiM. PlumbJ. LoppnauP. PizarroJ.C. SeitovaA. TrimbleW.S. SaftigP. GrinsteinS. Dhe-PaganonS. Structure of LIMP-2 provides functional insights with implications for SR-BI and CD36.Nature2013504747817217610.1038/nature12684 24162852
    [Google Scholar]
  9. KudaO. PietkaT.A. DemianovaZ. KudovaE. CvackaJ. KopeckyJ. AbumradN.A. Sulfo-N-succinimidyl oleate (SSO) inhibits fatty acid uptake and signaling for intracellular calcium via binding CD36 lysine 164: SSO also inhibits oxidized low density lipoprotein uptake by macrophages.J. Biol. Chem.201328822155471555510.1074/jbc.M113.473298 23603908
    [Google Scholar]
  10. ConradK.S. ChengT.W. YsselsteinD. HeybrockS. HothL.R. ChrunykB.A. am EndeC.W. KraincD. SchwakeM. SaftigP. LiuS. QiuX. EhlersM.D. Lysosomal integral membrane protein-2 as a phospholipid receptor revealed by biophysical and cellular studies.Nat. Commun.201781190810.1038/s41467‑017‑02044‑8 29199275
    [Google Scholar]
  11. GlatzJ.C. LuikenJ.F.P. Dynamic role of the transmembrane glycoprotein CD36 (SR-B2) in cellular fatty acid uptake and utilization.J. Lipid Res.20185971084109310.1194/jlr.R082933 29627764
    [Google Scholar]
  12. HeybrockS. KanervaK. MengY. IngC. LiangA. XiongZ.J. WengX. Ah KimY. CollinsR. TrimbleW. PomèsR. PrivéG.G. AnnaertW. SchwakeM. HeerenJ. Lüllmann-RauchR. GrinsteinS. IkonenE. SaftigP. NeculaiD. Lysosomal integral membrane protein-2 (LIMP-2/SCARB2) is involved in lysosomal cholesterol export.Nat. Commun.2019101352110.1038/s41467‑019‑11425‑0 31387993
    [Google Scholar]
  13. YuM. LauT.Y. CarrS.A. KriegerM. Contributions of a disulfide bond and a reduced cysteine side chain to the intrinsic activity of the high-density lipoprotein receptor SR-BI.Biochemistry20125150100441005510.1021/bi301203x 23205738
    [Google Scholar]
  14. ArmesillaA.L. VegaM.A. Structural organization of the gene for human CD36 glycoprotein.J. Biol. Chem.199426929189851899110.1016/S0021‑9258(17)32263‑9 7518447
    [Google Scholar]
  15. HaleJ.S. OtvosB. SinyukM. AlvaradoA.G. HitomiM. StoltzK. WuQ. FlavahanW. LevisonB. JohansenM.L. SchmittD. NeltnerJ.M. HuangP. RenB. SloanA.E. SilversteinR.L. GladsonC.L. DiDonatoJ.A. BrownJ.M. McIntyreT. HazenS.L. HorbinskiC. RichJ.N. LathiaJ.D. Cancer stem cell-specific scavenger receptor CD36 drives glioblastoma progression.Stem Cells20143271746175810.1002/stem.1716 24737733
    [Google Scholar]
  16. ParkY.M. FebbraioM. SilversteinR.L. CD36 modulates migration of mouse and human macrophages in response to oxidized LDL and may contribute to macrophage trapping in the arterial intima.J. Clin. Invest.20091191136145 19065049
    [Google Scholar]
  17. StuartL.M. BellS.A. StewartC.R. SilverJ.M. RichardJ. GossJ.L. TsengA.A. ZhangA. KhouryJ.B.E. MooreK.J. CD36 signals to the actin cytoskeleton and regulates microglial migration via a p130Cas complex.J. Biol. Chem.200728237273922740110.1074/jbc.M702887200 17623670
    [Google Scholar]
  18. PanJ. FanZ. WangZ. DaiQ. XiangZ. YuanF. YanM. ZhuZ. LiuB. LiC. CD36 mediates palmitate acid-induced metastasis of gastric cancer via AKT/GSK-3β/β-catenin pathway.J. Exp. Clin. Cancer Res.20193815210.1186/s13046‑019‑1049‑7 30717785
    [Google Scholar]
  19. XiaoY. YuD. Tumor microenvironment as a therapeutic target in cancer.Pharmacol. Ther.202122110775310.1016/j.pharmthera.2020.107753 33259885
    [Google Scholar]
  20. LiJ. ByrneK.T. YanF. YamazoeT. ChenZ. BaslanT. RichmanL.P. LinJ.H. SunY.H. RechA.J. BalliD. HayC.A. SelaY. MerrellA.J. LiudahlS.M. GordonN. NorgardR.J. YuanS. YuS. ChaoT. YeS. Eisinger-MathasonT.S.K. FaryabiR.B. TobiasJ.W. LoweS.W. CoussensL.M. WherryE.J. VonderheideR.H. StangerB.Z. Tumor cell-intrinsic factors underlie heterogeneity of immune cell infiltration and response to immunotherapy.Immunity2018491178193.e710.1016/j.immuni.2018.06.006 29958801
    [Google Scholar]
  21. MaW. ZhangK. BaoZ. JiangT. ZhangY. SAMD9 is relating with M2 macrophage and remarkable malignancy characters in low-grade glioma.Front. Immunol.20211265965910.3389/fimmu.2021.659659 33936093
    [Google Scholar]
  22. CorteseN. CarrieroR. LaghiL. MantovaniA. MarchesiF. Prognostic significance of tumor-associated macrophages: past, present and future.Semin. Immunol.20204810140810.1016/j.smim.2020.101408 32943279
    [Google Scholar]
  23. JiangX. WangJ. DengX. XiongF. ZhangS. GongZ. LiX. CaoK. DengH. HeY. LiaoQ. XiangB. ZhouM. GuoC. ZengZ. LiG. LiX. XiongW. The role of microenvironment in tumor angiogenesis.J. Exp. Clin. Cancer Res.202039120410.1186/s13046‑020‑01709‑5 32993787
    [Google Scholar]
  24. GyamfiJ. KimJ. ChoiJ. Cancer as a metabolic disorder.Int. J. Mol. Sci.2022233115510.3390/ijms23031155 35163079
    [Google Scholar]
  25. BrooksJ.M. MenezesA.N. IbrahimM. ArcherL. LalN. BagnallC.J. von ZeidlerS.V. ValentineH.R. SpruceR.J. BatisN. BryantJ.L. HartleyM. KaulB. RyanG.B. BaoR. KhattriA. LeeS.P. OgburekeK.U.E. MiddletonG. TennantD.A. BeggsA.D. DeeksJ. WestC.M.L. CazierJ.B. WillcoxB.E. SeiwertT.Y. MehannaH. Development and validation of a combined hypoxia and immune prognostic classifier for head and neck cancer.Clin. Cancer Res.201925175315532810.1158/1078‑0432.CCR‑18‑3314 31182433
    [Google Scholar]
  26. WoodsD.M. SodréA.L. VillagraA. SarnaikA. SotomayorE.M. WeberJ. HDAC inhibition upregulates PD-1 ligands in melanoma and augments immunotherapy with PD-1 blockade.Cancer Immunol. Res.20153121375138510.1158/2326‑6066.CIR‑15‑0077‑T 26297712
    [Google Scholar]
  27. BianX. LiuR. MengY. XingD. XuD. LuZ. Lipid metabolism and cancer.J. Exp. Med.20212181e2020160610.1084/jem.20201606 33601415
    [Google Scholar]
  28. KimD.H. SongN.Y. YimH. Targeting dysregulated lipid metabolism in the tumor microenvironment.Arch. Pharm. Res.20234611-1285588110.1007/s12272‑023‑01473‑y 38060103
    [Google Scholar]
  29. YuW. LeiQ. YangL. QinG. LiuS. WangD. PingY. ZhangY. Contradictory roles of lipid metabolism in immune response within the tumor microenvironment.J. Hematol. Oncol.202114118710.1186/s13045‑021‑01200‑4 34742349
    [Google Scholar]
  30. PittJ.M. MarabelleA. EggermontA. SoriaJ.C. KroemerG. ZitvogelL. Targeting the tumor microenvironment: Removing obstruction to anticancer immune responses and immunotherapy.Ann. Oncol.20162781482149210.1093/annonc/mdw168 27069014
    [Google Scholar]
  31. MuraiH. KodamaT. MaesakaK. TangeS. MotookaD. SuzukiY. ShigematsuY. InamuraK. MiseY. SaiuraA. OnoY. TakahashiY. KawasakiY. IinoS. KobayashiS. IdogawaM. TokinoT. Hashidate-YoshidaT. ShindouH. MiyazakiM. ImaiY. TanakaS. MitaE. OhkawaK. HikitaH. SakamoriR. TatsumiT. EguchiH. MoriiE. TakeharaT. Multiomics identifies the link between intratumor steatosis and the exhausted tumor immune microenvironment in hepatocellular carcinoma.Hepatology2023771779110.1002/hep.32573 35567547
    [Google Scholar]
  32. VinayD.S. RyanE.P. PawelecG. TalibW.H. StaggJ. ElkordE. LichtorT. DeckerW.K. WhelanR.L. KumaraH.M.C.S. SignoriE. HonokiK. GeorgakilasA.G. AminA. HelferichW.G. BoosaniC.S. GuhaG. CirioloM.R. ChenS. MohammedS.I. AzmiA.S. KeithW.N. BilslandA. BhaktaD. HalickaD. FujiiH. AquilanoK. AshrafS.S. NowsheenS. YangX. ChoiB.K. KwonB.S. Immune evasion in cancer: Mechanistic basis and therapeutic strategies.Semin. Cancer Biol.201535Suppl.S185S19810.1016/j.semcancer.2015.03.004 25818339
    [Google Scholar]
  33. de VisserK.E. JoyceJ.A. The evolving tumor microenvironment: From cancer initiation to metastatic outgrowth.Cancer Cell202341337440310.1016/j.ccell.2023.02.016 36917948
    [Google Scholar]
  34. JiangM. WuN. XuB. ChuY. LiX. SuS. ChenD. LiW. ShiY. GaoX. ZhangH. ZhangZ. DuW. NieY. LiangJ. FanD. Fatty acid-induced CD36 expression via O-GlcNAcylation drives gastric cancer metastasis.Theranostics20199185359537310.7150/thno.34024 31410220
    [Google Scholar]
  35. PascualG. AvgustinovaA. MejettaS. MartínM. CastellanosA. AttoliniC.S.O. BerenguerA. PratsN. TollA. HuetoJ.A. BescósC. Di CroceL. BenitahS.A. Targeting metastasis-initiating cells through the fatty acid receptor CD36.Nature20175417635414510.1038/nature20791 27974793
    [Google Scholar]
  36. YangP. SuC. LuoX. ZengH. ZhaoL. WeiL. ZhangX. VargheseZ. MoorheadJ.F. ChenY. RuanX.Z. Dietary oleic acid-induced CD36 promotes cervical cancer cell growth and metastasis via up-regulation Src/ERK pathway.Cancer Lett.2018438768510.1016/j.canlet.2018.09.006 30213558
    [Google Scholar]
  37. LiuL.Z. WangB. ZhangR. WuZ. HuangY. ZhangX. ZhouJ. YiJ. ShenJ. LiM.Y. DongM. The activated CD36-Src axis promotes lung adenocarcinoma cell proliferation and actin remodeling-involved metastasis in high-fat environment.Cell Death Dis.202314854810.1038/s41419‑023‑06078‑3 37612265
    [Google Scholar]
  38. LadanyiA. MukherjeeA. KennyH.A. JohnsonA. MitraA.K. SundaresanS. NiemanK.M. PascualG. BenitahS.A. MontagA. YamadaS.D. AbumradN.A. LengyelE. Adipocyte-induced CD36 expression drives ovarian cancer progression and metastasis.Oncogene201837172285230110.1038/s41388‑017‑0093‑z 29398710
    [Google Scholar]
  39. BratD.J. Castellano-SanchezA.A. HunterS.B. PecotM. CohenC. HammondE.H. DeviS.N. KaurB. Van MeirE.G. Pseudopalisades in glioblastoma are hypoxic, express extracellular matrix proteases, and are formed by an actively migrating cell population.Cancer Res.200464392092710.1158/0008‑5472.CAN‑03‑2073 14871821
    [Google Scholar]
  40. TaïbB. AboussalahA.M. MoniruzzamanM. ChenS. HaugheyN.J. KimS.F. AhimaR.S. Lipid accumulation and oxidation in glioblastoma multiforme.Sci. Rep.2019911959310.1038/s41598‑019‑55985‑z 31863022
    [Google Scholar]
  41. ShakyaS. GromovskyA.D. HaleJ.S. KnudsenA.M. PragerB. WallaceL.C. PenalvaL.O.F. BrownH.A. KristensenB.W. RichJ.N. LathiaJ.D. BrownJ.M. HubertC.G. Altered lipid metabolism marks glioblastoma stem and non-stem cells in separate tumor niches.Acta Neuropathol. Commun.20219110110.1186/s40478‑021‑01205‑7 34059134
    [Google Scholar]
  42. TanaseC. EnciuA.M. CodriciE. PopescuI.D. DudauM. DobriA.M. PopS. MihaiS. Gheorghișan-GălățeanuA.A. HinescuM.E. Fatty acids, CD36, thrombospondin-1, and CD47 in glioblastoma: together and/or separately?Int. J. Mol. Sci.202223260410.3390/ijms23020604 35054787
    [Google Scholar]
  43. YouZ. HuZ. HouC. MaC. XuX. ZhengY. SunX. KeY. LiangJ. XieZ. ShuL. LiuY. FABP4 facilitates epithelial-mesenchymal transition via elevating CD36 expression in glioma cells.Neoplasia20245710105010.1016/j.neo.2024.101050 39243502
    [Google Scholar]
  44. ZaouiM. MorelM. FerrandN. FellahiS. BastardJ.P. LamazièreA. LarsenA.K. BéréziatV. AtlanM. SabbahM. Breast-associated adipocytes secretome induce fatty acid uptake and invasiveness in breast cancer cells via CD36 independently of body mass index, menopausal status and mammary density.Cancers (Basel)20191112201210.3390/cancers11122012 31847105
    [Google Scholar]
  45. CascianoJ.C. PerryC. Cohen-NowakA.J. MillerK.D. Vande VoordeJ. ZhangQ. ChalmersS. SandisonM.E. LiuQ. HedleyA. McBryanT. TangH.Y. GormanN. BeerT. SpeicherD.W. AdamsP.D. LiuX. SchlegelR. McCarronJ.G. WakelamM.J.O. GottliebE. KossenkovA.V. SchugZ.T. MYC regulates fatty acid metabolism through a multigenic program in claudin-low triple negative breast cancer.Br. J. Cancer2020122686888410.1038/s41416‑019‑0711‑3 31942031
    [Google Scholar]
  46. WangC. HanJ. ChenY. Inhibition of CD36 and Nogo-B expression inhibited the proliferation and migration of triple negative breast cancer cells.Chin. J. Biotechnol.2023391041684188 37877398
    [Google Scholar]
  47. RybinskaI. ManganoN. Romero-CordobaS.L. RegondiV. CiravoloV. De CeccoL. MaffioliE. PaoliniB. BianchiF. SfondriniL. TedeschiG. AgrestiR. TagliabueE. TriulziT. SAA1 ‐dependent reprogramming of adipocytes by tumor cells is associated with triple negative breast cancer aggressiveness.Int. J. Cancer2024154101842185610.1002/ijc.34859 38289016
    [Google Scholar]
  48. YeH. AdaneB. KhanN. SullivanT. MinhajuddinM. GasparettoM. StevensB. PeiS. BalysM. AshtonJ.M. KlemmD.J. WoolthuisC.M. StranahanA.W. ParkC.Y. JordanC.T. Leukemic stem cells evade chemotherapy by metabolic adaptation to an adipose tissue niche.Cell Stem Cell2016191233710.1016/j.stem.2016.06.001 27374788
    [Google Scholar]
  49. FargeT. SalandE. de ToniF. ArouaN. HosseiniM. PerryR. BoscC. SugitaM. StuaniL. FraisseM. ScotlandS. LarrueC. BoutzenH. FéliuV. Nicolau-TraversM.L. Cassant-SourdyS. BroinN. DavidM. SerhanN. SarryA. TavitianS. KaomaT. VallarL. IacovoniJ. LinaresL.K. MontersinoC. CastellanoR. GriessingerE. ColletteY. DuchampO. BarreiraY. HirschP. PalamaT. GalesL. DelhommeauF. Garmy-SusiniB.H. PortaisJ.C. VergezF. SelakM. Danet-DesnoyersG. CarrollM. RécherC. SarryJ.E. Chemotherapy-resistant human acute myeloid leukemia cells are not enriched for leukemic stem cells but require oxidative metabolism.Cancer Discov.20177771673510.1158/2159‑8290.CD‑16‑0441 28416471
    [Google Scholar]
  50. ZhangY. GuoH. ZhangZ. LuW. ZhuJ. ShiJ. IL-6 promotes chemoresistance via upregulating CD36 mediated fatty acids uptake in acute myeloid leukemia.Exp. Cell Res.2022415111311210.1016/j.yexcr.2022.113112 35346671
    [Google Scholar]
  51. FengW.W. WilkinsO. BangS. UngM. LiJ. AnJ. del GenioC. CanfieldK. DiRenzoJ. WellsW. GaurA. RobeyR.B. GuoJ.Y. PowlesR.L. SotiriouC. PusztaiL. FebbraioM. ChengC. KinlawW.B. KurokawaM. CD36-mediated metabolic rewiring of breast cancer cells promotes resistance to HER2-targeted therapies.Cell Rep.2019291134053420.e510.1016/j.celrep.2019.11.008 31825825
    [Google Scholar]
  52. YangL. SunJ. LiM. LongY. ZhangD. GuoH. HuangR. YanJ. Oxidized low-density lipoprotein links hypercholesterolemia and bladder cancer aggressiveness by promoting cancer stemness.Cancer Res.202181225720573210.1158/0008‑5472.CAN‑21‑0646 34479964
    [Google Scholar]
  53. GyamfiJ. YeoJ.H. KwonD. MinB.S. ChaY.J. KooJ.S. JeongJ. LeeJ. ChoiJ. Interaction between CD36 and FABP4 modulates adipocyte-induced fatty acid import and metabolism in breast cancer.NPJ Breast Cancer20217112910.1038/s41523‑021‑00324‑7 34561446
    [Google Scholar]
  54. FridmanW.H. PagèsF. Sautès-FridmanC. GalonJ. The immune contexture in human tumours: impact on clinical outcome.Nat. Rev. Cancer201212429830610.1038/nrc3245 22419253
    [Google Scholar]
  55. FarhoodB. NajafiM. MortezaeeK. CD8+ cytotoxic T lymphocytes in cancer immunotherapy: A review.J. Cell. Physiol.201923468509852110.1002/jcp.27782 30520029
    [Google Scholar]
  56. ChowA. PericaK. KlebanoffC.A. WolchokJ.D. Clinical implications of T cell exhaustion for cancer immunotherapy.Nat. Rev. Clin. Oncol.2022191277579010.1038/s41571‑022‑00689‑z 36216928
    [Google Scholar]
  57. ManzoT. PrenticeB.M. AndersonK.G. RamanA. SchalckA. CodreanuG.S. Nava LausonC.B. TibertiS. RaimondiA. JonesM.A. ReyzerM. BatesB.M. SpragginsJ.M. PattersonN.H. McLeanJ.A. RaiK. TacchettiC. TucciS. WargoJ.A. RodighieroS. Clise-DwyerK. SherrodS.D. KimM. NavinN.E. CaprioliR.M. GreenbergP.D. DraettaG. NeziL. Accumulation of long-chain fatty acids in the tumor microenvironment drives dysfunction in intrapancreatic CD8+ T cells.J. Exp. Med.20202178e2019192010.1084/jem.20191920 32491160
    [Google Scholar]
  58. AoY.Q. GaoJ. ZhangL.X. DengJ. WangS. LinM. WangH.K. DingJ.Y. JiangJ.H. Tumor-infiltrating CD36+CD8+T cells determine exhausted tumor microenvironment and correlate with inferior response to chemotherapy in non-small cell lung cancer.BMC Cancer202323136710.1186/s12885‑023‑10836‑z 37085798
    [Google Scholar]
  59. XuS. ChaudharyO. Rodríguez-MoralesP. SunX. ChenD. ZappasodiR. XuZ. PintoA.F.M. WilliamsA. SchulzeI. FarsakogluY. VaranasiS.K. LowJ.S. TangW. WangH. McDonaldB. TrippleV. DownesM. EvansR.M. AbumradN.A. MerghoubT. WolchokJ.D. ShokhirevM.N. HoP.C. WitztumJ.L. EmuB. CuiG. KaechS.M. Uptake of oxidized lipids by the scavenger receptor CD36 promotes lipid peroxidation and dysfunction in CD8+ T cells in tumors.Immunity202154715611577.e710.1016/j.immuni.2021.05.003 34102100
    [Google Scholar]
  60. MaX. XiaoL. LiuL. YeL. SuP. BiE. WangQ. YangM. QianJ. YiQ. CD36-mediated ferroptosis dampens intratumoral CD8+ T cell effector function and impairs their antitumor ability.Cell Metab.202133510011012.e510.1016/j.cmet.2021.02.015 33691090
    [Google Scholar]
  61. CD36 activity causes ferroptosis in tumor-infiltrating CD8+ T cells.Cancer Discov.2021115OF2410.1158/2159‑8290.CD‑RW2021‑039 33741707
    [Google Scholar]
  62. KoloninM.G. Bad cholesterol uptake by CD36 in T-cells cripples anti-tumor immune response.Immunometabolism (Cobham)202134e21002810.20900/immunometab20210028 34603769
    [Google Scholar]
  63. OrangeJ.S. Formation and function of the lytic NK-cell immunological synapse.Nat. Rev. Immunol.20088971372510.1038/nri2381 19172692
    [Google Scholar]
  64. SchimmerS. MittermüllerD. WernerT. GörsP.E. MeckelmannS.W. FinlayD.K. DittmerU. Littwitz-SalomonE. Fatty acids are crucial to fuel NK cells upon acute retrovirus infection.Front. Immunol.202314129635510.3389/fimmu.2023.1296355 38094304
    [Google Scholar]
  65. HuX. JiaX. XuC. WeiY. WangZ. LiuG. YouQ. LuG. GongW. Downregulation of NK cell activities in Apolipoprotein C-III-induced hyperlipidemia resulting from lipid-induced metabolic reprogramming and crosstalk with lipid-laden dendritic cells.Metabolism202112015480010.1016/j.metabol.2021.154800 34051224
    [Google Scholar]
  66. GowdaN.M. WuX. KumarS. FebbraioM. GowdaD.C. CD36 contributes to malaria parasite-induced pro-inflammatory cytokine production and NK and T cell activation by dendritic cells.PLoS One2013810e7760410.1371/journal.pone.0077604 24204889
    [Google Scholar]
  67. NiavaraniS.R. LawsonC. BakosO. BoudaudM. BatenchukC. RouleauS. TaiL.H. Lipid accumulation impairs natural killer cell cytotoxicity and tumor control in the postoperative period.BMC Cancer201919182310.1186/s12885‑019‑6045‑y 31429730
    [Google Scholar]
  68. SavageP.A. KlawonD.E.J. MillerC.H. Regulatory T cell development.Annu. Rev. Immunol.202038142145310.1146/annurev‑immunol‑100219‑020937 31990619
    [Google Scholar]
  69. SharmaP. Hu-LieskovanS. WargoJ.A. RibasA. Primary, adaptive, and acquired resistance to cancer immunotherapy.Cell2017168470772310.1016/j.cell.2017.01.017 28187290
    [Google Scholar]
  70. RechA.J. MickR. MartinS. RecioA. AquiN.A. PowellD.J.Jr ColligonT.A. TroskoJ.A. LeinbachL.I. PletcherC.H. TweedC.K. DeMicheleA. FoxK.R. DomchekS.M. RileyJ.L. VonderheideR.H. CD25 blockade depletes and selectively reprograms regulatory T cells in concert with immunotherapy in cancer patients.Sci. Transl. Med.20124134134ra6210.1126/scitranslmed.3003330 22593175
    [Google Scholar]
  71. SutmullerR.P.M. van DuivenvoordeL.M. van ElsasA. SchumacherT.N.M. WildenbergM.E. AllisonJ.P. ToesR.E.M. OffringaR. MeliefC.J.M. Synergism of cytotoxic T lymphocyte-associated antigen 4 blockade and depletion of CD25(+) regulatory T cells in antitumor therapy reveals alternative pathways for suppression of autoreactive cytotoxic T lymphocyte responses.J. Exp. Med.2001194682383210.1084/jem.194.6.823 11560997
    [Google Scholar]
  72. WangH. FrancoF. TsuiY.C. XieX. TrefnyM.P. ZappasodiR. MohmoodS.R. Fernández-GarcíaJ. TsaiC.H. SchulzeI. PicardF. MeylanE. SilversteinR. GoldbergI. FendtS.M. WolchokJ.D. MerghoubT. JandusC. ZippeliusA. HoP.C. CD36-mediated metabolic adaptation supports regulatory T cell survival and function in tumors.Nat. Immunol.202021329830810.1038/s41590‑019‑0589‑5 32066953
    [Google Scholar]
  73. MiaoY. ZhangC. YangL. ZengX. HuY. XueX. DaiY. WeiZ. The activation of PPARγ enhances Treg responses through up-regulating CD36/CPT1-mediated fatty acid oxidation and subsequent N-glycan branching of TβRII/IL-2Rα.Cell Commun. Signal.20222014810.1186/s12964‑022‑00849‑9 35392915
    [Google Scholar]
  74. GeysL. VranckxC. LijnenH.R. ScroyenI. CD36 deficiency blunts effects of diet on regulatory T cells in murine gonadal adipose tissue and mesenteric lymph nodes.Cell. Immunol.20152981-2333610.1016/j.cellimm.2015.08.006 26344897
    [Google Scholar]
  75. SalmaninejadA. ValilouS.F. SoltaniA. AhmadiS. AbarghanY.J. RosengrenR.J. SahebkarA. Tumor-associated macrophages: role in cancer development and therapeutic implications.Cell Oncol. (Dordr.)201942559160810.1007/s13402‑019‑00453‑z 31144271
    [Google Scholar]
  76. GaoJ. LiangY. WangL. Shaping polarization of tumor-associated macrophages in cancer immunotherapy.Front. Immunol.20221388871310.3389/fimmu.2022.888713 35844605
    [Google Scholar]
  77. PanY. YuY. WangX. ZhangT. Tumor-associated macrophages in tumor immunity.Front. Immunol.20201158308410.3389/fimmu.2020.583084 33365025
    [Google Scholar]
  78. MosserD.M. EdwardsJ.P. Exploring the full spectrum of macrophage activation.Nat. Rev. Immunol.200881295896910.1038/nri2448 19029990
    [Google Scholar]
  79. CornK.C. WindhamM.A. RafatM. Lipids in the tumor microenvironment: From cancer progression to treatment.Prog. Lipid Res.20208010105510.1016/j.plipres.2020.101055 32791170
    [Google Scholar]
  80. HuangS.C.C. EvertsB. IvanovaY. O’SullivanD. NascimentoM. SmithA.M. BeattyW. Love-GregoryL. LamW.Y. O’NeillC.M. YanC. DuH. AbumradN.A. UrbanJ.F.Jr ArtyomovM.N. PearceE.L. PearceE.J. Cell-intrinsic lysosomal lipolysis is essential for alternative activation of macrophages.Nat. Immunol.201415984685510.1038/ni.2956 25086775
    [Google Scholar]
  81. ChenY. YangM. HuangW. ChenW. ZhaoY. SchulteM.L. VolberdingP. GerbecZ. ZimmermannM.T. ZeighamiA. DemosW. ZhangJ. KnaackD.A. SmithB.C. CuiW. MalarkannanS. SodhiK. ShapiroJ.I. XieZ. SahooD. SilversteinR.L. Mitochondrial metabolic reprogramming by CD36 signaling drives macrophage inflammatory responses.Circ. Res.2019125121087110210.1161/CIRCRESAHA.119.315833 31625810
    [Google Scholar]
  82. SuP. WangQ. BiE. MaX. LiuL. YangM. QianJ. YiQ. Enhanced lipid accumulation and metabolism are required for the differentiation and activation of tumor-associated macrophages.Cancer Res.20208071438145010.1158/0008‑5472.CAN‑19‑2994 32015091
    [Google Scholar]
  83. AlbakriM.M. HuangS.C.C. TashkandiH.N. SiegS.F. Fatty acids secreted from head and neck cancer induce M2-like Macrophages.J. Leukoc. Biol.2022112461762810.1002/JLB.1A0521‑251R 35213745
    [Google Scholar]
  84. YangP. QinH. LiY. XiaoA. ZhengE. ZengH. SuC. LuoX. LuQ. LiaoM. ZhaoL. WeiL. VargheseZ. MoorheadJ.F. ChenY. RuanX.Z. CD36-mediated metabolic crosstalk between tumor cells and macrophages affects liver metastasis.Nat. Commun.2022131578210.1038/s41467‑022‑33349‑y 36184646
    [Google Scholar]
  85. AguirreL.A. Montalbán-HernándezK. Avendaño-OrtizJ. MarínE. LozanoR. ToledanoV. Sánchez-MarotoL. TerrónV. ValentínJ. PulidoE. CasalvillaJ.C. RubioC. DiekhorstL. Laso-GarcíaF. del FresnoC. Collazo-LorduyA. Jiménez-MunarrizB. Gómez-CampeloP. Llanos-GonzálezE. Fernández-VelascoM. Rodríguez-AntolínC. Pérez de DiegoR. Cantero-CidR. Hernádez-JimenezE. ÁlvarezE. RosasR. dies López-AyllónB. de CastroJ. WculekS.K. Cubillos-ZapataC. Ibáñez de CáceresI. Díaz-AgeroP. Gutiérrez FernándezM. Paz de MiguelM. SanchoD. SchulteL. PeronaR. Belda-IniestaC. BoscáL. López-CollazoE. Tumor stem cells fuse with monocytes to form highly invasive tumor-hybrid cells.OncoImmunology202091177320410.1080/2162402X.2020.1773204 32923132
    [Google Scholar]
  86. DorhoiA. Du PlessisN. Monocytic myeloid-derived suppressor cells in chronic infections.Front. Immunol.20188189510.3389/fimmu.2017.01895 29354120
    [Google Scholar]
  87. ChristofidesA. StraussL. YeoA. CaoC. CharestA. BoussiotisV.A. The complex role of tumor-infiltrating macrophages.Nat. Immunol.20222381148115610.1038/s41590‑022‑01267‑2 35879449
    [Google Scholar]
  88. ParkerK.H. BeuryD.W. Ostrand-RosenbergS. Myeloid-derived suppressor cells.Adv. Cancer Res.20151289513910.1016/bs.acr.2015.04.002 26216631
    [Google Scholar]
  89. SicaA. MassarottiM. Myeloid suppressor cells in cancer and autoimmunity.J. Autoimmun.20178511712510.1016/j.jaut.2017.07.010 28728794
    [Google Scholar]
  90. AdeshakinA.O. LiuW. AdeshakinF.O. AfolabiL.O. ZhangM. ZhangG. WangL. LiZ. LinL. CaoQ. YanD. WanX. Regulation of ROS in myeloid-derived suppressor cells through targeting fatty acid transport protein 2 enhanced anti-PD-L1 tumor immunotherapy.Cell. Immunol.202136210428610.1016/j.cellimm.2021.104286 33524739
    [Google Scholar]
  91. Al-KhamiA.A. ZhengL. Del ValleL. HossainF. WyczechowskaD. ZabaletaJ. SanchezM.D. DeanM.J. RodriguezP.C. OchoaA.C. Exogenous lipid uptake induces metabolic and functional reprogramming of tumor-associated myeloid-derived suppressor cells.OncoImmunology2017610e134480410.1080/2162402X.2017.1344804 29123954
    [Google Scholar]
  92. KalluriR. The biology and function of fibroblasts in cancer.Nat. Rev. Cancer201616958259810.1038/nrc.2016.73 27550820
    [Google Scholar]
  93. ÖhlundD. ElyadaE. TuvesonD. Fibroblast heterogeneity in the cancer wound.J. Exp. Med.201421181503152310.1084/jem.20140692 25071162
    [Google Scholar]
  94. MaC. YangC. PengA. SunT. JiX. MiJ. WeiL. ShenS. FengQ. Pan-cancer spatially resolved single-cell analysis reveals the crosstalk between cancer-associated fibroblasts and tumor microenvironment.Mol. Cancer202322117010.1186/s12943‑023‑01876‑x 37833788
    [Google Scholar]
  95. MaoX. XuJ. WangW. LiangC. HuaJ. LiuJ. ZhangB. MengQ. YuX. ShiS. Crosstalk between cancer-associated fibroblasts and immune cells in the tumor microenvironment: new findings and future perspectives.Mol. Cancer202120113110.1186/s12943‑021‑01428‑1 34635121
    [Google Scholar]
  96. NathA. ChanC. Genetic alterations in fatty acid transport and metabolism genes are associated with metastatic progression and poor prognosis of human cancers.Sci. Rep.2016611866910.1038/srep18669 26725848
    [Google Scholar]
  97. XiaoZ. ToddL. HuangL. Noguera-OrtegaE. LuZ. HuangL. KoppM. LiY. PattadaN. ZhongW. GuoW. SchollerJ. LiousiaM. AssenmacherC.A. JuneC.H. AlbeldaS.M. PuréE. Desmoplastic stroma restricts T cell extravasation and mediates immune exclusion and immunosuppression in solid tumors.Nat. Commun.2023141511010.1038/s41467‑023‑40850‑5 37607999
    [Google Scholar]
  98. ZhuG.Q. TangZ. HuangR. QuW.F. FangY. YangR. TaoC.Y. GaoJ. WuX.L. SunH.X. ZhouY.F. SongS.S. DingZ.B. DaiZ. ZhouJ. YeD. WuD.J. LiuW.R. FanJ. ShiY.H. CD36+ cancer-associated fibroblasts provide immunosuppressive microenvironment for hepatocellular carcinoma via secretion of macrophage migration inhibitory factor.Cell Discov.2023912510.1038/s41421‑023‑00529‑z 36878933
    [Google Scholar]
  99. GongJ. LinY. ZhangH. LiuC. ChengZ. YangX. ZhangJ. XiaoY. SangN. QianX. WangL. CenX. DuX. ZhaoY. Reprogramming of lipid metabolism in cancer-associated fibroblasts potentiates migration of colorectal cancer cells.Cell Death Dis.202011426710.1038/s41419‑020‑2434‑z 32327627
    [Google Scholar]
  100. NanP. DongX. BaiX. LuH. LiuF. SunY. ZhaoX. Tumor-stroma TGF-β1-THBS2 feedback circuit drives pancreatic ductal adenocarcinoma progression via integrin αvβ3/CD36-mediated activation of the MAPK pathway.Cancer Lett.2022528597510.1016/j.canlet.2021.12.025 34958892
    [Google Scholar]
  101. ZhangL. BilletS. GonzalesG. Rohena-RiveraK. MuranakaH. ChuG. YangQ. KimH. BhowmickN. SmithB. Fatty acid signaling impacts prostate cancer lineage plasticity in an autocrine and paracrine manner.Cancers (Basel)20221414344910.3390/cancers14143449 35884514
    [Google Scholar]
  102. JayawardhanaA.M.D.S. StilgenbauerM. DattaP. QiuZ. MckenzieS. WangH. BowersD. KurokawaM. ZhengY.R. Fatty acid-like Pt(IV) prodrugs overcome cisplatin resistance in ovarian cancer by harnessing CD36.Chem. Commun. (Camb.)20205673107061070910.1039/D0CC02174A 32789350
    [Google Scholar]
  103. WangB. YanN. WuD. DouY. LiuZ. HuX. ChenC. Combination inhibition of triple-negative breast cancer cell growth with CD36 siRNA-loaded DNA nanoprism and genistein.Nanotechnology2021323939510110.1088/1361‑6528/ac0d1e 34153956
    [Google Scholar]
  104. SpN. KangD. KimD. ParkJ. LeeH. KimH. DarvinP. ParkY.M. YangY. Nobiletin inhibits CD36-dependent tumor angiogenesis, migration, invasion, and sphere formation through the Cd36/Stat3/Nf-Κb signaling axis.Nutrients201810677210.3390/nu10060772 29914089
    [Google Scholar]
  105. ChenL. XiaJ.S. WuJ.H. ChenY.G. QiuC.J. Quercetin suppresses cell survival and invasion in oral squamous cell carcinoma via the miR-1254/CD36 cascade in vitro.Hum. Exp. Toxicol.20214091413142110.1177/0960327121991912 33686878
    [Google Scholar]
  106. PangB. XuX. LuY. JinH. YangR. JiangC. ShaoD. LiuY. ShiJ. Prediction of new targets and mechanisms for quercetin in the treatment of pancreatic cancer, colon cancer, and rectal cancer.Food Funct.20191095339534910.1039/C9FO01168D 31393490
    [Google Scholar]
  107. ChenX. WangL. WuY. SongS. MinH. YangY. HeX. LiangQ. YiL. WangY. GaoQ. Effect of puerarin in promoting fatty acid oxidation by increasing mitochondrial oxidative capacity and biogenesis in skeletal muscle in diabetic rats.Nutr. Diabetes201881110.1038/s41387‑017‑0009‑6 29330446
    [Google Scholar]
  108. MahalingamD. HarbW. PatnaikA. BullockA. WatnickR.S. VincentM.Y. ChenJ.J. WangS. PestanaH. ChaoJ. MahoneyJ. CieslewiczM. WatnickJ. First-in-human phase I dose escalation trial of the first-in-class tumor microenvironment modulator VT1021 in advanced solid tumors.Commun. Med.2024411010.1038/s43856‑024‑00433‑x 38218979
    [Google Scholar]
  109. ChenJ.J. VincentM.Y. ShepardD. PeereboomD. MahalingamD. BattisteJ. PatelM.R. JuricD. WenP.Y. BullockA. SelfridgeJ.E. PantS. LiuJ. LiW. FyfeS. WangS. ZotaV. MahoneyJ. WatnickR.S. CieslewiczM. WatnickJ. Phase 1 dose expansion and biomarker study assessing first-in-class tumor microenvironment modulator VT1021 in patients with advanced solid tumors.Commun. Med.2024419510.1038/s43856‑024‑00520‑z 38773224
    [Google Scholar]
  110. FebbraioM. AbumradN.A. HajjarD.P. SharmaK. ChengW. PearceS.F.A. SilversteinR.L. A null mutation in murine CD36 reveals an important role in fatty acid and lipoprotein metabolism.J. Biol. Chem.199927427190551906210.1074/jbc.274.27.19055 10383407
    [Google Scholar]
  111. KajiharaS. HisatomiA. OgawaY. YasutakeT. YoshimuraT. HaraT. MizutaT. OzakiI. IwamotoN. YamamotoK. Association of the Pro90Ser CD36 mutation with elevated free fatty acid concentrations but not with insulin resistance syndrome in Japanese.Clin. Chim. Acta20013141-212513010.1016/S0009‑8981(01)00658‑1 11718687
    [Google Scholar]
  112. MiyaokaK. KuwasakoT. HiranoK. NozakiS. YamashitaS. MatsuzawaY. CD36 deficiency associated with insulin resistance.Lancet2001357925768668710.1016/S0140‑6736(00)04138‑6 11247555
    [Google Scholar]
  113. KuwasakoT. HiranoK. SakaiN. IshigamiM. HiraokaH. YakubM.J. Yamauchi-TakiharaK. YamashitaS. MatsuzawaY. Lipoprotein abnormalities in human genetic CD36 deficiency associated with insulin resistance and abnormal fatty acid metabolism.Diabetes Care20032651647164810.2337/diacare.26.5.1647‑a 12716848
    [Google Scholar]
  114. HiranoK. KuwasakoT. Nakagawa-ToyamaY. JanabiM. YamashitaS. MatsuzawaY. Pathophysiology of human genetic CD36 deficiency.Trends Cardiovasc. Med.200313413614110.1016/S1050‑1738(03)00026‑4 12732446
    [Google Scholar]
  115. YamashitaS. HiranoK.I. KuwasakoT. JanabiM. ToyamaY. IshigamiM. SakaiN. Physiological and pathological roles of a multi-ligand receptor CD36 in atherogenesis; Insights from CD36-deficient patients.Mol. Cell. Biochem.20072991-2192210.1007/s11010‑005‑9031‑4 16670819
    [Google Scholar]
  116. DomínguezD.J. EnríquezS. AlbaG. GarnachoC. CorteganaC. CamposR. MerinoL. HajjiN. Sánchez-MargaletV. PrietoL. Cancer nano-immunotherapy: The novel and promising weapon to fight cancer.Int. J. Mol. Sci.2024252119510.3390/ijms25021195 38256268
    [Google Scholar]
  117. GuoS. FengJ. LiZ. YangS. QiuX. XuY. ShenZ. Improved cancer immunotherapy strategies by nanomedicine.Wiley Interdiscip. Rev. Nanomed. Nanobiotechnol.2023153e187310.1002/wnan.1873 36576112
    [Google Scholar]
  118. ShiY. LammersT. Combining nanomedicine and immunotherapy.Acc. Chem. Res.20195261543155410.1021/acs.accounts.9b00148 31120725
    [Google Scholar]
  119. BaiY. NanY. WuT. ZhuA. XieX. SunY. DengY. DouZ. HuX. ZhouR. XuS. ZhangY. FanJ. JuD. Lipid nanoparticle‐mediated delivery of CRISPR‐Cas9 against rubicon ameliorates nafld by modulating CD36 along with glycerophospholipid metabolism.Adv. Sci.20241131240049310.1002/advs.202400493 38894572
    [Google Scholar]
  120. ZhaoN. FrancisN.L. SongS. KholodovychV. CalvelliH.R. HoopC.L. PangZ.P. BaumJ. UhrichK.E. MogheP.V. CD36‐binding amphiphilic nanoparticles for attenuation of α‐synuclein‐induced microglial activation.Adv. NanoBiomed Res.202226210012010.1002/anbr.202100120 36051821
    [Google Scholar]
  121. ZhangJ. NieS. ZuY. AbbasiM. CaoJ. LiC. WuD. LabibS. BrackeeG. ShenC.L. WangS. Anti-atherogenic effects of CD36-targeted epigallocatechin gallate-loaded nanoparticles.J. Control. Release201930326327310.1016/j.jconrel.2019.04.018 30999008
    [Google Scholar]
  122. CuiK. GaoX. WangB. WuH. ArulsamyK. DongY. XiaoY. JiangX. MalovichkoM.V. LiK. PengQ. LuY.W. ZhuB. ZhengR. WongS. CowanD.B. LintonM. SrivastavaS. ShiJ. ChenK. ChenH. Epsin nanotherapy regulates cholesterol transport to fortify atheroma regression.Circ. Res.20231321e22e4210.1161/CIRCRESAHA.122.321723 36444722
    [Google Scholar]
  123. GaoC. HuangQ. LiuC. KwongC.H.T. YueL. WanJ.B. LeeS.M.Y. WangR. Treatment of atherosclerosis by macrophage-biomimetic nanoparticles via targeted pharmacotherapy and sequestration of proinflammatory cytokines.Nat. Commun.2020111262210.1038/s41467‑020‑16439‑7 32457361
    [Google Scholar]
  124. WilsonC.G. TranJ.L. ErionD.M. VeraN.B. FebbraioM. WeissE.J. Hepatocyte-specific disruption of cd36 attenuates fatty liver and improves insulin sensitivity in HFD-fed mice.Endocrinology2016157257058510.1210/en.2015‑1866 26650570
    [Google Scholar]
  125. MarleauS. HarbD. BujoldK. AvalloneR. IkenK. WangY. DemersA. SiroisM.G. FebbraioM. SilversteinR.L. TremblayA. OngH. EP 80317, a ligand of the CD36 scavenger receptor, protects apolipoprotein E‐deficient mice from developing atherosclerotic lesions.FASEB J.200519131869187110.1096/fj.04‑3253fje 16123174
    [Google Scholar]
  126. BujoldK. MellalK. ZoccalK.F. RhaindsD. BrissetteL. FebbraioM. MarleauS. OngH. EP 80317, a CD36 selective ligand, promotes reverse cholesterol transport in apolipoprotein E-deficient mice.Atherosclerosis2013229240841410.1016/j.atherosclerosis.2013.05.031 23880196
    [Google Scholar]
  127. GeloenA. HelinL. GeeraertB. MalaudE. HolvoetP. MarguerieG. CD36 inhibitors reduce postprandial hypertriglyceridemia and protect against diabetic dyslipidemia and atherosclerosis.PLoS One201275e3763310.1371/journal.pone.0037633 22662181
    [Google Scholar]
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