Overcoming Chemoimmunotherapy-Induced Immunosuppression by Assemblable and Depot Forming Immune Modulating Nanosuspension.

Item request has been placed! ×
Item request cannot be made. ×
loading   Processing Request
Read More Add to Saved list
  • Additional Information
    • Source:
      Publisher: WILEY-VCH Country of Publication: Germany NLM ID: 101664569 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2198-3844 (Electronic) Linking ISSN: 21983844 NLM ISO Abbreviation: Adv Sci (Weinh) Subsets: MEDLINE
    • Publication Information:
      Original Publication: Weinheim : WILEY-VCH, [2014]-
    • Subject Terms:
      Breast Neoplasms/*drug therapy ; Breast Neoplasms/*immunology ; Immunosuppression Therapy/*methods ; Immunotherapy/*methods ; Nanomedicine/*methods; Animals ; Disease Models, Animal ; Immunotherapy/adverse effects
    • Abstract:
      The deficiency of antigen-specific T cells and the induction of various treatment-induced immunosuppressions still limits the clinical benefit of cancer immunotherapy. Although the chemo-immunotherapy adjuvanted with Toll-like receptor 7/8 agonist (TLR 7/8a) induces immunogenic cell death (ICD) and in situ vaccination effect, indoleamine 2,3-dioxygenase (IDO) is also significantly increased in the tumor microenvironment (TME) and tumor-draining lymph node (TDLN), which offsets the activated antitumor immunity. To address the treatment-induced immunosuppression, an assemblable immune modulating suspension (AIMS) containing ICD inducer (paclitaxel) and supra-adjuvant (immune booster; R848 as a TLR 7/8a, immunosuppression reliever; epacadostat as an IDO inhibitor) is suggested and shows that it increases cytotoxic T lymphocytes and relieves the IDO-related immunosuppression (TGF-β, IL-10, myeloid-derived suppressor cells, and regulatory T cells) in both TME and TDLN, by the formation of in situ depot in tumor bed as well as by the efficient migration into TDLN. Local administration of AIMS increases T cell infiltration in both local and distant tumors and significantly inhibits the metastasis of tumors to the lung. Reverting treatment-induced secondary immunosuppression and reshaping "cold tumor" into "hot tumor" by AIMS also increases the response rate of immune checkpoint blockade therapy, which promises a new nanotheranostic strategy in cancer immunotherapy.
      (© 2021 The Authors. Advanced Science published by Wiley-VCH GmbH.)
    • References:
      Nat Rev Immunol. 2018 Mar;18(3):168-182. (PMID: 29226910)
      Nat Rev Immunol. 2001 Nov;1(2):135-45. (PMID: 11905821)
      Cancer Res. 2018 Oct 15;78(20):5891-5900. (PMID: 30104241)
      Trends Immunol. 2013 Mar;34(3):137-43. (PMID: 23103127)
      J Clin Invest. 2007 Sep;117(9):2570-82. (PMID: 17710230)
      ACS Nano. 2019 Nov 26;13(11):12671-12686. (PMID: 31589013)
      Cancers (Basel). 2015 Dec 03;7(4):2360-71. (PMID: 26633515)
      Front Immunol. 2019 Feb 08;10:168. (PMID: 30800125)
      Nat Rev Drug Discov. 2015 Aug;14(8):561-84. (PMID: 26228759)
      Nat Rev Microbiol. 2007 Jul;5(7):505-17. (PMID: 17558426)
      Clin Exp Vaccine Res. 2014 Jul;3(2):113-6. (PMID: 25003083)
      Wiley Interdiscip Rev Nanomed Nanobiotechnol. 2019 Jan;11(1):e1524. (PMID: 29667346)
      Trends Immunol. 2016 Mar;37(3):193-207. (PMID: 26839260)
      Cancer Res. 2019 Sep 15;79(18):4557-4566. (PMID: 31350295)
      Cancer Res. 2017 Feb 15;77(4):817-822. (PMID: 28159861)
      J Clin Invest. 2007 May;117(5):1147-54. (PMID: 17476344)
      Front Immunol. 2018 Jan 31;9:151. (PMID: 29445380)
      Cancer Lett. 2018 Dec 1;438:17-23. (PMID: 30217563)
      Semin Immunol. 2018 Oct;39:14-21. (PMID: 29801750)
      Arterioscler Thromb Vasc Biol. 2005 Sep;25(9):1910-6. (PMID: 15994440)
      Front Immunol. 2018 Dec 11;9:2909. (PMID: 30619273)
      Expert Rev Vaccines. 2013 Jul;12(7):809-19. (PMID: 23885825)
      J Immunol. 2014 Mar 15;192(6):2722-33. (PMID: 24532579)
      Vaccine. 2016 Aug 5;34(36):4304-12. (PMID: 27402566)
      Adv Sci (Weinh). 2021 Oct;8(19):e2102043. (PMID: 34363349)
      J Cell Mol Med. 2019 Aug;23(8):4854-4865. (PMID: 31210425)
      Trends Cancer. 2018 Jan;4(1):38-58. (PMID: 29413421)
      J Hematol Oncol. 2018 Aug 2;11(1):100. (PMID: 30068361)
      Vaccine. 2009 Nov 16;27(49):6959-65. (PMID: 19751689)
      Front Cell Dev Biol. 2019 Nov 27;7:306. (PMID: 31828071)
      Nat Biotechnol. 2007 Oct;25(10):1159-64. (PMID: 17873867)
      Onco Targets Ther. 2019 Nov 11;12:9527-9538. (PMID: 31807028)
      Nat Med. 2018 May;24(5):541-550. (PMID: 29686425)
      Crit Rev Oncol Hematol. 2017 Aug;116:116-124. (PMID: 28693793)
      J Immunother Cancer. 2015 Dec 15;3:51. (PMID: 26674411)
      Nat Rev Immunol. 2004 Jul;4(7):499-511. (PMID: 15229469)
      Nat Rev Immunol. 2006 Jun;6(6):476-83. (PMID: 16691244)
      Nat Rev Immunol. 2004 Oct;4(10):762-74. (PMID: 15459668)
      Front Pharmacol. 2018 Aug 06;9:878. (PMID: 30127747)
      Immunity. 2010 Oct 29;33(4):492-503. (PMID: 21029960)
      Cancer Res. 2017 Dec 15;77(24):6795-6811. (PMID: 29247038)
      J Gen Virol. 2000 Nov;81(Pt 11):2605-2609. (PMID: 11038370)
      Science. 2018 Mar 23;359(6382):1350-1355. (PMID: 29567705)
      Science. 2015 Apr 3;348(6230):56-61. (PMID: 25838373)
      Front Pharmacol. 2017 May 31;8:304. (PMID: 28620298)
      Biochim Biophys Acta Rev Cancer. 2019 Apr;1871(2):199-224. (PMID: 30605718)
      Nat Commun. 2019 Aug 20;10(1):3745. (PMID: 31431623)
    • Grant Information:
      SRC-2017R1A5A1014560 National Research Foundation of Korea; NRF-2018M3A9H4078701 National Research Foundation of Korea; NRF-2020R1A2C3006888 National Research Foundation of Korea
    • Contributed Indexing:
      Keywords: adjuvants; drug delivery; immunosuppression; immunotherapy; tumor microenvironment
    • Publication Date:
      Date Created: 20210807 Date Completed: 20220211 Latest Revision: 20240928
    • Publication Date:
      20240928
    • Accession Number:
      PMC8498862
    • Accession Number:
      10.1002/advs.202102043
    • Accession Number:
      34363349