دورية أكاديمية
أعرض في EDS

Intratumoral administration of the Toll-like receptor 7/8 agonist 3M-052 enhances interferon-driven tumor immunogenicity and suppresses metastatic spread in preclinical triple-negative breast cancer.

التفاصيل البيبلوغرافية
العنوان: Intratumoral administration of the Toll-like receptor 7/8 agonist 3M-052 enhances interferon-driven tumor immunogenicity and suppresses metastatic spread in preclinical triple-negative breast cancer.
المؤلفون: Zanker DJ; Sir Peter MacCallum Department of Oncology University of Melbourne Parkville VIC Australia.; Cancer Immunology and Therapeutics Programs Peter MacCallum Cancer Centre Melbourne VIC Australia., Spurling AJ; Cancer Immunology and Therapeutics Programs Peter MacCallum Cancer Centre Melbourne VIC Australia., Brockwell NK; Sir Peter MacCallum Department of Oncology University of Melbourne Parkville VIC Australia.; Cancer Immunology and Therapeutics Programs Peter MacCallum Cancer Centre Melbourne VIC Australia., Owen KL; Sir Peter MacCallum Department of Oncology University of Melbourne Parkville VIC Australia.; Cancer Immunology and Therapeutics Programs Peter MacCallum Cancer Centre Melbourne VIC Australia., Zakhour JM; Department of Biochemistry and Genetics La Trobe Institute for Molecular Science La Trobe University Melbourne VIC Australia., Robinson T; Department of Biochemistry and Genetics La Trobe Institute for Molecular Science La Trobe University Melbourne VIC Australia., Duivenvoorden HM; Department of Biochemistry and Genetics La Trobe Institute for Molecular Science La Trobe University Melbourne VIC Australia.; School of Biological Sciences Monash University Clayton VIC Australia., Hertzog PJ; Centre for Innate Immunity and Infectious Diseases Hudson Institute of Medical Research Clayton VIC Australia., Mullins SR; R&D Oncology AstraZeneca Ltd Cambridge UK., Wilkinson RW; R&D Oncology AstraZeneca Ltd Cambridge UK., Parker BS; Sir Peter MacCallum Department of Oncology University of Melbourne Parkville VIC Australia.; Cancer Immunology and Therapeutics Programs Peter MacCallum Cancer Centre Melbourne VIC Australia.; Department of Biochemistry and Genetics La Trobe Institute for Molecular Science La Trobe University Melbourne VIC Australia.
المصدر: Clinical & translational immunology [Clin Transl Immunology] 2020 Sep 28; Vol. 9 (9), pp. e1177. Date of Electronic Publication: 2020 Sep 28 (Print Publication: 2020).
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: John Wiley & Sons Australia, Ltd. on behalf of Australasian Society for Immunology Inc Country of Publication: Australia NLM ID: 101638268 Publication Model: eCollection Cited Medium: Print ISSN: 2050-0068 (Print) Linking ISSN: 20500068 NLM ISO Abbreviation: Clin Transl Immunology Subsets: PubMed not MEDLINE
أسماء مطبوعة: Publication: 2018- : [Milton, Queensland] : John Wiley & Sons Australia, Ltd. on behalf of Australasian Society for Immunology Inc.
Original Publication: [London] : Nature Publishing Group, 2012-
مستخلص: Objectives: Loss of tumor-inherent type I interferon (IFN) signalling has been closely linked to accelerated metastatic progression via decreased immunogenicity and antitumor immunity. Previous studies in murine models of triple-negative breast cancer (TNBC) demonstrate that systemic IFN inducers are effective antimetastatic agents, via sustained antitumor CD8 + T-cell responses. Repeated systemic dosing with recombinant IFNs or IFN inducers is associated with significant toxicities; hence, the use of alternate intratumoral agents is an active area of investigation. It is critical to investigate the impact of intratumoral agents on subsequent metastatic spread to predict clinical impact.
Methods: In this study, the local and systemic impact of the intratumoral Toll-like receptor (TLR) 7/8 agonist 3M-052 alone or in combination with anti-PD1 was evaluated in metastatic TNBC models. The IFN-α receptor (IFNAR1) blocking antibody, MAR1-5A3, along with immune-deficient mice and ex vivo assays are utilised to examine the key targets of this agent that are critical for an antimetastatic response.
Results: Single intratumoral administration of 3M-052 reduced mammary tumor growth, induced a T-cell-inflamed tumor microenvironment (TME) and reduced metastatic spread to lung. Metastasis suppression was reliant on IFN signalling and an antitumor immune response, in contrast to primary tumor growth inhibition, which was retained in NSG and CD8 + T-cell-depleted mice. 3M-052 action was demonstrated via dendritic cell activation and production of type I IFN and other pro-inflammatory cytokines to initiate a T-cell-inflamed TME and promote tumor cell antigen presentation.
Conclusion: This work supports neoadjuvant TLR agonist-based immunotherapeutics as realistic options for immune activation in the TME and long-term metastatic protection in TNBC.
Competing Interests: Financial support and reagents were provided by AstraZeneca. SRM and RWW are employed by AstraZeneca Ltd.
(© 2020 The Authors. Clinical & Translational Immunology published by John Wiley & Sons Australia, Ltd on behalf of Australian and New Zealand Society for Immunology, Inc.)
References: J Immunol Methods. 1983 Dec 16;65(1-2):55-63. (PMID: 6606682)
J Natl Cancer Inst. 1976 Sep;57(3):599-602. (PMID: 978771)
J Immunol. 2012 May 15;188(10):4866-75. (PMID: 22504644)
EMBO Rep. 2020 Jun 4;21(6):e50162. (PMID: 32314873)
Nat Med. 2002 Aug;8(8):793-800. (PMID: 12091876)
CSH Protoc. 2008 Dec 01;2008:pdb.prot5080. (PMID: 21356739)
Nat Commun. 2018 Jan 16;9(1):248. (PMID: 29339738)
Cancer Cell. 2017 Feb 13;31(2):194-207. (PMID: 28196594)
Cancer Res. 1979 May;39(5):1645-50. (PMID: 371793)
Nat Med. 2014 Nov;20(11):1301-9. (PMID: 25344738)
Cancer Discov. 2016 Dec;6(12):1382-1399. (PMID: 27663893)
Cell Rep. 2015 May 19;11(7):1018-30. (PMID: 25959818)
Cancer Immunol Res. 2017 Oct;5(10):871-884. (PMID: 28848054)
Nat Med. 2012 Aug;18(8):1224-31. (PMID: 22820642)
J Exp Med. 2011 Nov 21;208(12):2357-66. (PMID: 22065672)
Trends Immunol. 2016 Nov;37(11):724-737. (PMID: 27614798)
J Biol Response Mod. 1985 Apr;4(2):129-33. (PMID: 3998763)
Cancer Biol Ther. 2020 Jul 2;21(7):629-636. (PMID: 32378445)
J Exp Med. 2011 Sep 26;208(10):1989-2003. (PMID: 21930769)
Nat Med. 2018 Jul;24(7):986-993. (PMID: 29942092)
Blood. 2002 May 1;99(9):3263-71. (PMID: 11964292)
Eur J Immunol. 2001 Nov;31(11):3388-93. (PMID: 11745357)
Nat Rev Cancer. 2016 Mar;16(3):131-44. (PMID: 26911188)
PLoS One. 2012;7(10):e46989. (PMID: 23071691)
J Bone Miner Res. 1997 Sep;12(9):1387-95. (PMID: 9286754)
Breast Cancer Res. 2015 Sep 04;17:124. (PMID: 26341640)
Ann Oncol. 2014 Aug;25(8):1544-50. (PMID: 24608200)
Adv Exp Med Biol. 2017;1036:19-31. (PMID: 29275462)
Breast Cancer Res Treat. 2000 Nov;64(2):189-91. (PMID: 11194454)
Cancer Discov. 2014 Jun;4(6):674-87. (PMID: 24589924)
Proc Natl Acad Sci U S A. 2008 Nov 25;105(47):18490-5. (PMID: 19001271)
J Immunol Methods. 1999 Feb 1;223(1):77-92. (PMID: 10037236)
J Immunol. 2005 Oct 15;175(8):5043-9. (PMID: 16210607)
Clin Exp Metastasis. 1999 Mar;17(2):163-70. (PMID: 10411109)
Nucleic Acids Res. 2013 Jan;41(Database issue):D1040-6. (PMID: 23203888)
J Immunol. 2013 Apr 1;190(7):3783-97. (PMID: 23440412)
Cancer Res. 2011 Aug 1;71(15):5123-33. (PMID: 21697281)
Proc Natl Acad Sci U S A. 2009 Apr 28;106(17):7119-24. (PMID: 19359475)
Immunol Cell Biol. 2018 Oct;96(9):981-993. (PMID: 29738610)
J Clin Oncol. 2019 Mar 1;37(7):559-569. (PMID: 30650045)
J Clin Oncol. 1986 Feb;4(2):234-43. (PMID: 2418169)
Nat Immunol. 2002 Jun;3(6):499. (PMID: 12032557)
Cold Spring Harb Protoc. 2010 Jun;2010(6):pdb.prot5439. (PMID: 20516177)
J Immunol. 2013 Jul 1;191(1):52-9. (PMID: 23709680)
Sci Transl Med. 2018 Mar 21;10(433):. (PMID: 29563317)
J Exp Med. 2001 Sep 17;194(6):863-9. (PMID: 11561001)
NPJ Precis Oncol. 2019 Aug 29;3:21. (PMID: 31482136)
Annu Rev Immunol. 2013;31:443-73. (PMID: 23298205)
Ann Oncol. 1990;1(2):150-1. (PMID: 2078495)
JCI Insight. 2018 Nov 15;3(22):. (PMID: 30429378)
Nat Immunol. 2002 Feb;3(2):196-200. (PMID: 11812998)
Cell. 2014 Oct 23;159(3):499-513. (PMID: 25417103)
Sci Immunol. 2017 Apr 14;2(10):. (PMID: 28738020)
Lancet. 1980 Jul 26;2(8187):161-4. (PMID: 6105336)
J Immunother Cancer. 2019 Sep 11;7(1):244. (PMID: 31511088)
Oncol Rep. 2003 Nov-Dec;10(6):2005-8. (PMID: 14534734)
Immunology. 1997 Jul;91(3):421-9. (PMID: 9301532)
Proc Soc Exp Biol Med. 1951 Jun;77(2):358-62. (PMID: 14854049)
J Immunol Methods. 2013 Jan 31;387(1-2):173-80. (PMID: 23098837)
J Immunol. 2011 Mar 1;186(5):2772-9. (PMID: 21263073)
Eur J Cancer. 2017 Feb;72:95-102. (PMID: 28027521)
Cell Immunol. 2002 Jul-Aug;218(1-2):74-86. (PMID: 12470615)
Vaccine. 2011 Jul 26;29(33):5434-42. (PMID: 21641953)
J Exp Med. 2013 Mar 11;210(3):491-502. (PMID: 23460726)
J Immunol. 2009 Sep 15;183(6):3652-60. (PMID: 19710468)
J Exp Med. 1999 Feb 1;189(3):521-30. (PMID: 9927514)
Cell. 2015 Aug 27;162(5):974-86. (PMID: 26317466)
فهرسة مساهمة: Keywords: CD8+ T cell; TLR agonist; immunotherapy; interferon; metastasis; triple‐negative breast cancer
تواريخ الأحداث: Date Created: 20201002 Latest Revision: 20220417
رمز التحديث: 20240829
مُعرف محوري في PubMed: PMC7520806
DOI: 10.1002/cti2.1177
PMID: 33005415
قاعدة البيانات: MEDLINE
الوصف
تدمد:2050-0068
DOI:10.1002/cti2.1177