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Volume 30, Issue 31
  • ISSN: 1381-6128
  • E-ISSN: 1873-4286

Abstract

Introduction

Cancer is an individual disease and its formation and development are specific to each host. Conventional treatments are ineffective in complex cases, such as metastasis, and have severe adverse side effects. New strategies are needed to address the problem, and the use of immunogenic cell death (ICD) as a trigger or booster of the immune system through the exposure of damage-associated molecular patterns, along with tumor antigens, by cancerous cells is presented as an immunization approach in this work.

Methods

For this purpose, 4T1 cells were exposed to doxorubicin (DOX) for 24 hours and then, these cells undergoing ICD were subcutaneously administered to mice. The ICD induction by DOX on 4T1 was assessed by flow cytometry and image analysis. This immunization process was performed three times and after the last administration, the immunized mice were challenged with a subcutaneous xenograft of live cancer cells.

Results

The results demonstrate that the mice immunized with cells undergoing ICD after exposure to DOX presented no primary tumor or indications of distant metastatic lesion development.

Conclusion

In summary, our findings indicate that the immunization process utilizing ICD is indeed efficacious in managing this aggressive form of pre-clinical breast cancer.

© 2024 Bentham Science Publishers
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2024-07-22
2024-11-16

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References

  1. HanahanD WeinbergRA Hallmarks of cancer: The next generation.Cell20111445646674
     [Google Scholar]
  2. HanahanD WeinbergRA The hallmarks of cancer.Cell200010015760
     [Google Scholar]
  3. HanahanD. Hallmarks of cancer: New dimensions.Cancer Discov.2022121314610.1158/2159‑8290.CD‑21‑105935022204
     [Google Scholar]
  4. RodriguesM.C. MoraisJ.A.V. GanassinR. OliveiraG.R.T. CostaF.C. MoraisA.A.C. SilveiraA.P. SilvaV.C.M. LongoJ.P.F. MuehlmannL.A. An overview on immunogenic cell death in cancer biology and therapy.Pharmaceutics2022148156410.3390/pharmaceutics1408156436015189
     [Google Scholar]
  5. SteegP.S. Targeting metastasis.Nat. Rev. Cancer201616420121810.1038/nrc.2016.2527009393
     [Google Scholar]
  6. NardinS. MoraE. VarugheseF.M. D’AvanzoF. VachanaramA.R. RossiV. SaggiaC. RubinelliS. GennariA. Breast cancer survivorship, quality of life, and late toxicities.Front. Oncol.20201086410.3389/fonc.2020.0086432612947
     [Google Scholar]
  7. RodriguesM.C. de Sousa JúniorW.T. MundimT. ValeC.L.C. de OliveiraJ.V. GanassinR. PachecoT.J.A. Vasconcelos MoraisJ.A. LongoJ.P.F. AzevedoR.B. MuehlmannL.A. Induction of immunogenic cell death by photodynamic therapy mediated by aluminum-phthalocyanine in nanoemulsion.Pharmaceutics202214119610.3390/pharmaceutics1401019635057091
     [Google Scholar]
  8. GargAD Dudek-PericAM RomanoE AgostinisP Immunogenic cell death.Int. J. Dev. Biol.2015591-2-313114010.1387/ijdb.150061pa
     [Google Scholar]
  9. KryskoD.V. GargA.D. KaczmarekA. KryskoO. AgostinisP. VandenabeeleP. Immunogenic cell death and DAMPs in cancer therapy.Nat. Rev. Cancer2012121286087510.1038/nrc338023151605
     [Google Scholar]
  10. de LimaL.I. FariaR.S. FrancoM.S. RoqueM.C. Arruda PachecoT.J. RodriguesM.C. MuehlmannL.A. MoyaS.E. AzevedoR.B. de OliveiraM.C. Figueiró LongoJ.P. Combined paclitaxel-doxorubicin liposomal results in positive prognosis with infiltrating lymphocytes in lung metastasis.Nanomedicine202015282753277010.2217/nnm‑2020‑020133179587
     [Google Scholar]
  11. VasconcelosM.J.A. The induction of immunogenic cell death by photodynamic therapy in B16F10 cells in vitro is affected by the concentration of the photosensitizer.Photodiagn. Photodyn. Ther.2021102392
     [Google Scholar]
  12. LongoJ. MuehlmannL. Almeida-SantosM. AzevedoR. Preventing metastasis by targeting lymphatic vessels with photodynamic therapy based on nanostructured photosensitizers.J. Nanomed. Nanotechnol.2015651
     [Google Scholar]
  13. LuJ. LiuX. LiaoY.P. WangX. AhmedA. JiangW. JiY. MengH. NelA.E. Breast cancer chemo-immunotherapy through liposomal delivery of an immunogenic cell death stimulus plus interference in the IDO-1 pathway.ACS Nano20181211110411106110.1021/acsnano.8b0518930481959
     [Google Scholar]
  14. RenX. WangN. ZhouY. SongA. JinG. LiZ. LuanY. An injectable hydrogel using an immunomodulating gelator for amplified tumor immunotherapy by blocking the arginase pathway.Acta Biomater.202112417919010.1016/j.actbio.2021.01.04133524560
     [Google Scholar]
  15. RodriguesM.C. VieiraL.G. HorstF.H. de AraújoE.C. GanassinR. MerkerC. MeyerT. BöttnerJ. VenusT. LongoJ.P.F. ChavesS.B. GarciaM.P. Estrela-LopisI. AzevedoR.B. MuehlmannL.A. Photodynamic therapy mediated by aluminium-phthalocyanine nanoemulsion eliminates primary tumors and pulmonary metastases in a murine 4T1 breast adenocarcinoma model.J. Photochem. Photobiol. B202020411180810.1016/j.jphotobiol.2020.11180832006892
     [Google Scholar]
  16. dos Santos CâmaraA.L. NagelG. TschicheH.R. CardadorC.M. MuehlmannL.A. de OliveiraD.M. AlvimP.Q. AzevedoR.B. CalderónM. Figueiró LongoJ.P. Acid-sensitive lipidated doxorubicin prodrug entrapped in nanoemulsion impairs lung tumor metastasis in a breast cancer model.Nanomedicine201712151751176510.2217/nnm‑2017‑009128703043
     [Google Scholar]
  17. da RochaM.C.O. da SilvaP.B. RadicchiM.A. AndradeB.Y.G. de OliveiraJ.V. VenusT. MerkerC. Estrela-LopisI. LongoJ.P.F. BáoS.N. Docetaxel-loaded solid lipid nanoparticles prevent tumor growth and lung metastasis of 4T1 murine mammary carcinoma cells.J. Nanobiotechnol20201814310.1186/s12951‑020‑00604‑732164731
     [Google Scholar]
  18. TsengJ.C. KungA.L. In vivo imaging of inflammatory phagocytes.Chem. Biol.20121991199120910.1016/j.chembiol.2012.08.00722999887
     [Google Scholar]
  19. SantosD.S. MoraisJ.A.V. VanderleiÍ.A.C. SantosA.S. AzevedoR.B. MuehlmannL.A. JúniorO.R.P. MortariM.R. da SilvaJ.R. da SilvaS.W. LongoJ.P.F. Oral delivery of fish oil in oil-in-water nanoemulsion: Development, colloidal stability and modulatory effect on in vivo inflammatory induction in mice.Biomed. Pharmacother.202113311098010.1016/j.biopha.2020.11098033249282
     [Google Scholar]
  20. SilvaG.S. SilvaD.A. GuilhelmelliF. JerônimoM.S. Cardoso-MiguelM.R.D. BürgelP.H. CastroR.J.A. de OliveiraS A M. Silva-PereiraI. BoccaA.L. TavaresA.H. Zymosan enhances in vitro phagocyte function and the immune response of mice infected with Paracoccidioides brasiliensis.Med. Mycol.202159874976210.1093/mmy/myaa11733550415
     [Google Scholar]
  21. Cardoso-MiguelM.R.D. BürgelP.H. de CastroR.J.A. MarinaC.L. de OliveiraS.A. AlbuquerqueP. Silva-PereiraI. BoccaA.L. TavaresA.H. Dectin-2 is critical for phagocyte function and resistance to Paracoccidioides brasiliensis in mice.Med. Mycol.20236111myad11710.1093/mmy/myad11737960963
     [Google Scholar]
  22. KaiserJ. Taking a shot at cancer.Science2022376658912612910.1126/science.abq373835389791
     [Google Scholar]
  23. LongoJ.P.F. MuehlmannL.A. Application of nanomedicine in immunotherapy: Recent advances and prospects.Pharmaceutics2023157191010.3390/pharmaceutics1507191037514096
     [Google Scholar]
  24. YuR. ZhaoF. XuZ. ZhangG. DuB. ShuQ. Current status and future of cancer vaccines: A bibliographic study.Heliyon2024102e2440410.1016/j.heliyon.2024.e2440438293405
     [Google Scholar]
  25. SayourE. Mendez-GomezH. MitchellD. Cancer vaccine immunotherapy with RNA-loaded liposomes.Int. J. Mol. Sci.20181910289010.3390/ijms1910289030249040
     [Google Scholar]
  26. CardadorC.M. MuehlmannL.A. CoelhoC.M. SilvaL.P. GarayA.V. CarvalhoA.M.S. BastosI.M.D. LongoJ.P.F. Nucleotides entrapped in liposome nanovesicles as tools for therapeutic and diagnostic use in biomedical applications.Pharmaceutics202315387310.3390/pharmaceutics1503087336986734
     [Google Scholar]
  27. CapiciS. AmmoniL.C. MeliN. CogliatiV. PepeF.F. PiazzaF. CazzanigaM.E. Personalised therapies for metastatic triple-negative breast cancer: When target is not everything.Cancers20221415372910.3390/cancers1415372935954393
     [Google Scholar]
  28. Miranda-VilelaA.L. GrisoliaC.K. LongoJ.P.F. PeixotoR.C.A. de AlmeidaM.C. BarbosaL.C.P. RollM.M. PortilhoF.A. EstevanatoL.L.C. BoccaA.L. BáoS.N. LacavaZ.G.M. Oil rich in carotenoids instead of vitamins C and E as a better option to reduce doxorubicin-induced damage to normal cells of Ehrlich tumor-bearing mice: Hematological, toxicological and histopathological evaluations.J. Nutr. Biochem.201425111161117610.1016/j.jnutbio.2014.06.00525127291
     [Google Scholar]
  29. GustafsonD.L. RastatterJ.C. ColomboT. LongM.E. Doxorubicin pharmacokinetics: Macromolecule binding, metabolism, and excretion in the context of a physiologic model.J. Pharm. Sci.20029161488150110.1002/jps.1016112115848
     [Google Scholar]
  30. LongoJ.P.F. MuehlmannL.A. Miranda-VilelaA.L. PortilhoF.A. de SouzaL.R. SilvaJ.R. LacavaZ.G.M. BoccaA.L. ChavesS.B. AzevedoR.B. Prevention of distant lung metastasis after photodynamic therapy application in a breast cancer tumor model.J. Biomed. Nanotechnol.201612468969910.1166/jbn.2016.220827301195
     [Google Scholar]
  31. de AndradeL.R. TedescoA.C. PrimoF.L. FariasG.R. da SilvaJ.R. LongoJ.P.F. de AlmeidaM.C. de SouzaP.E.N. de AzevedoR.B. PinheiroW.O. LacavaZ.G.M. Tumor cell death in orthotopic breast cancer model by NanoALA: A novel perspective on photodynamic therapy in oncology.Nanomedicine202015101019103610.2217/nnm‑2019‑045832264766
     [Google Scholar]
  32. PulaskiBA Ostrand-RosenbergS Mouse 4T1 breast tumor model.Curr. Protoc. Immunol.2000391116
     [Google Scholar]
  33. CoelhoJ.M. CamargoN.S. GanassinR. RochaM.C.O. MerkerC. BöttnerJ. Estrela-LopisI. Py-DanielK.R. JardimK.V. SousaM.H. OmbredaneA.S. JoanittiG.A. SilvaR.C. AzevedoR.B. LongoJ.P.F. MuehlmannL.A. Oily core/amphiphilic polymer shell nanocapsules change the intracellular fate of doxorubicin in breast cancer cells.J. Mater. Chem. B Mater. Biol. Med.20197416390639810.1039/C9TB00587K31642844
     [Google Scholar]
  34. GanassinR. MerkerC. RodriguesM.C. GuimarãesN.F. SodréC.S.C. FerreiraQ.D.S. da SilvaS.W. OmbredaneA.S. JoanittiG.A. Py-DanielK.R. ZhangJ. JiangC.S. de MoraisP.C. Mosiniewicz-SzablewskaE. SuchockiP. LongoJ.P.F. MeijerJ. Estrela-LopisI. de AzevedoR.B. MuehlmannL.A. Nanocapsules for the co-delivery of selol and doxorubicin to breast adenocarcinoma 4T1 cells in vitro.Artif. Cells Nanomed. Biotechnol.20184682002201229179603
     [Google Scholar]
  35. MussiS.V. SilvaR.C. OliveiraM.C. LucciC.M. AzevedoR.B. FerreiraL.A.M. New approach to improve encapsulation and antitumor activity of doxorubicin loaded in solid lipid nanoparticles.Eur. J. Pharm. Sci.2013481-228229010.1016/j.ejps.2012.10.02523178339
     [Google Scholar]
  36. ObeidM. TesniereA. GhiringhelliF. FimiaG.M. ApetohL. PerfettiniJ.L. CastedoM. MignotG. PanaretakisT. CasaresN. MétivierD. LarochetteN. van EndertP. CiccosantiF. PiacentiniM. ZitvogelL. KroemerG. Calreticulin exposure dictates the immunogenicity of cancer cell death.Nat. Med.2007131546110.1038/nm152317187072
     [Google Scholar]
  37. PanH. LiuP. ZhaoL. PanY. MaoM. KroemerG. Immunogenic cell stress and death in the treatment of cancer.Seminars in Cell & Developmental Biology.Elsevier2024
     [Google Scholar]
  38. RadicchiM.A. de OliveiraJ.V. MendesA.C.P. de OliveiraD.M. MuehlmannL.A. MoraisP.C. AzevedoR.B. LongoJ.P.F. Lipid nanoemulsion passive tumor accumulation dependence on tumor stage and anatomical location: A new mathematical model for in vivo imaging biodistribution studies.J. Mater. Chem. B Mater. Biol. Med.20186447306731610.1039/C8TB01577E32254640
     [Google Scholar]
  39. SeongJ. KimK. Activation of cellular players in adaptive immunity via exogenous delivery of tumor cell lysates.Pharmaceutics2022147135810.3390/pharmaceutics1407135835890254
     [Google Scholar]
  40. de OliveiraJV Oliveira da RochaMC de Sousa-JuniorAA RodriguesMC FariasGR da SilvaPB Tumor vascular heterogeneity and the impact of subtumoral nanoemulsion biodistribution. Nanomedicine 2023172720732088
     [Google Scholar]
  41. IlkovitchD. LopezD.M. The liver is a site for tumor-induced myeloid-derived suppressor cell accumulation and immunosuppression.Cancer Res.200969135514552110.1158/0008‑5472.CAN‑08‑462519549903
     [Google Scholar]
  42. AlizadehD. TradM. HankeN.T. LarmonierC.B. JanikashviliN. BonnotteB. KatsanisE. LarmonierN. Doxorubicin eliminates myeloid-derived suppressor cells and enhances the efficacy of adoptive T-cell transfer in breast cancer.Cancer Res.201474110411810.1158/0008‑5472.CAN‑13‑154524197130
     [Google Scholar]
  43. Diaz-MonteroC.M. SalemM.L. NishimuraM.I. Garrett-MayerE. ColeD.J. MonteroA.J. Increased circulating myeloid-derived suppressor cells correlate with clinical cancer stage, metastatic tumor burden, and doxorubicin–cyclophosphamide chemotherapy.Cancer Immunol. Immunother.2009581495910.1007/s00262‑008‑0523‑418446337
     [Google Scholar]
  44. GabrilovichD.I. NagarajS. Myeloid-derived suppressor cells as regulators of the immune system.Nat. Rev. Immunol.20099316217410.1038/nri250619197294
     [Google Scholar]
  45. LeesJ.G. WhiteD. KeatingB.A. Barkl-LukeM.E. MakkerP.G.S. GoldsteinD. Moalem-TaylorG. Oxaliplatin-induced haematological toxicity and splenomegaly in mice.PLoS One2020159e023816410.1371/journal.pone.023816432877416
     [Google Scholar]
  46. ParrettaE. CasseseG. BarbaP. SantoniA. GuardiolaJ. Di RosaF. CD8 cell division maintaining cytotoxic memory occurs predominantly in the bone marrow.J. Immunol.2005174127654766410.4049/jimmunol.174.12.765415944266
     [Google Scholar]
  47. KimH.J. CantorH. CD4 T-cell subsets and tumor immunity: The helpful and the not-so-helpful.Cancer Immunol. Res.201422919810.1158/2326‑6066.CIR‑13‑021624778273
     [Google Scholar]
  48. OhD.Y. FongL. Cytotoxic CD4+ T cells in cancer: Expanding the immune effector toolbox.Immunity202154122701271110.1016/j.immuni.2021.11.01534910940
     [Google Scholar]
  49. WangH. NajibiA.J. SobralM.C. SeoB.R. LeeJ.Y. WuD. LiA.W. VerbekeC.S. MooneyD.J. Biomaterial-based scaffold for in situ chemo-immunotherapy to treat poorly immunogenic tumors.Nat. Commun.2020111569610.1038/s41467‑020‑19540‑z33173046
     [Google Scholar]
  50. WeigeltB. PeterseJ.L. van’t VeerL.J. Breast cancer metastasis: Markers and models.Nat. Rev. Cancer20055859160210.1038/nrc167016056258
     [Google Scholar]
  51. LongoJ.P.F. de MeloL.N.D. MijanM.C. ValoisC.R.A. JoanittiG.A. SimioniA.R. TedescoA.C. de AzevedoR.B. Photodynamic therapy mediated by liposomal chloroaluminum-phthalocyanine induces necrosis in oral cancer cells.J. Biomater. Tissue Eng.20133114815610.1166/jbt.2013.1070
     [Google Scholar]
/content/journals/cpd/10.2174/0113816128316870240610045550
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Doxorubicin-induced Immunogenic Cell Death Impairs Tumor Progression and Distant Metastasis in a 4T1 Breast Cancer Tumor Model
Curr. Pharm. Des. 30, 2493 (2024); https://doi.org/10.2174/0113816128316870240610045550
/content/journals/cpd/10.2174/0113816128316870240610045550
/content/journals/cpd/10.2174/0113816128316870240610045550
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  • Article Type:     Research Article
Keyword(s): breast cancer, tumor progression, molecular patterns; immunization; immunogenic cell death; Metastasis

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