دورية أكاديمية
أعرض في EDS

Deleting the mitochondrial respiration negative regulator MCJ enhances the efficacy of CD8 + T cell adoptive therapies in pre-clinical studies.

التفاصيل البيبلوغرافية
العنوان: Deleting the mitochondrial respiration negative regulator MCJ enhances the efficacy of CD8 + T cell adoptive therapies in pre-clinical studies.
المؤلفون: Wu MH; Department of Immunology and Microbiology, University of Colorado, Anschutz Medical Campus, Aurora, CO, USA., Valenca-Pereira F; Department of Immunology and Microbiology, University of Colorado, Anschutz Medical Campus, Aurora, CO, USA., Cendali F; Department of Biochemistry and Molecular Genetics, University of Colorado Anschutz Medical Campus, Aurora, CO, USA., Giddings EL; Division of Immunobiology, Department of Medicine, Larner College of Medicine, University of Vermont, Burlington, VT, USA., Pham-Danis C; Department of Pediatric Hematology, Oncology and Bone Marrow Transplant, University of Colorado, Anschutz Medical Campus, Aurora, CO, USA., Yarnell MC; Department of Pediatric Hematology, Oncology and Bone Marrow Transplant, University of Colorado, Anschutz Medical Campus, Aurora, CO, USA., Novak AJ; Department of Pediatric Hematology, Oncology and Bone Marrow Transplant, University of Colorado, Anschutz Medical Campus, Aurora, CO, USA., Brunetti TM; Department of Immunology and Microbiology, University of Colorado, Anschutz Medical Campus, Aurora, CO, USA., Thompson SB; Department of Immunology and Microbiology, University of Colorado, Anschutz Medical Campus, Aurora, CO, USA., Henao-Mejia J; Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA, USA.; Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.; Division of Transplant Immunology, Department of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia, University of Pennsylvania, Philadelphia, PA, USA., Flavell RA; Department of Immunobiology, School of Medicine, Yale University, New Haven, CT, USA.; Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT, USA., D'Alessandro A; Department of Biochemistry and Molecular Genetics, University of Colorado Anschutz Medical Campus, Aurora, CO, USA., Kohler ME; Department of Pediatric Hematology, Oncology and Bone Marrow Transplant, University of Colorado, Anschutz Medical Campus, Aurora, CO, USA. Mark.Kohler@cuanschutz.edu.; Center for Cancer and Blood Disorders, Children's Hospital Colorado, Aurora, CO, USA. Mark.Kohler@cuanschutz.edu., Rincon M; Department of Immunology and Microbiology, University of Colorado, Anschutz Medical Campus, Aurora, CO, USA. Mercedes.Rincon@cuanschutz.edu.; Division of Immunobiology, Department of Medicine, Larner College of Medicine, University of Vermont, Burlington, VT, USA. Mercedes.Rincon@cuanschutz.edu.
المصدر: Nature communications [Nat Commun] 2024 May 24; Vol. 15 (1), pp. 4444. Date of Electronic Publication: 2024 May 24.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Nature Pub. Group Country of Publication: England NLM ID: 101528555 Publication Model: Electronic Cited Medium: Internet ISSN: 2041-1723 (Electronic) Linking ISSN: 20411723 NLM ISO Abbreviation: Nat Commun Subsets: MEDLINE
أسماء مطبوعة: Original Publication: [London] : Nature Pub. Group
مواضيع طبية MeSH: CD8-Positive T-Lymphocytes*/immunology , CD8-Positive T-Lymphocytes*/metabolism , Mitochondria*/metabolism , Immunotherapy, Adoptive*/methods, Animals ; Humans ; Mice ; Mice, Inbred C57BL ; Mitochondrial Proteins/metabolism ; Mitochondrial Proteins/genetics ; Cell Respiration ; Cell Line, Tumor ; Female ; Ovalbumin/immunology ; Melanoma, Experimental/immunology ; Melanoma, Experimental/therapy
مستخلص: Mitochondrial respiration is essential for the survival and function of T cells used in adoptive cellular therapies. However, strategies that specifically enhance mitochondrial respiration to promote T cell function remain limited. Here, we investigate methylation-controlled J protein (MCJ), an endogenous negative regulator of mitochondrial complex I expressed in CD8 cells, as a target for improving the efficacy of adoptive T cell therapies. We demonstrate that MCJ inhibits mitochondrial respiration in murine CD8 + CAR-T cells and that deletion of MCJ increases their in vitro and in vivo efficacy against murine B cell leukaemia. Similarly, MCJ deletion in ovalbumin (OVA)-specific CD8 + T cells also increases their efficacy against established OVA-expressing melanoma tumors in vivo. Furthermore, we show for the first time that MCJ is expressed in human CD8 cells and that the level of MCJ expression correlates with the functional activity of CD8 + CAR-T cells. Silencing MCJ expression in human CD8 CAR-T cells increases their mitochondrial metabolism and enhances their anti-tumor activity. Thus, targeting MCJ may represent a potential therapeutic strategy to increase mitochondrial metabolism and improve the efficacy of adoptive T cell therapies.
(© 2024. The Author(s).)
References: Immunity. 2012 Jan 27;36(1):68-78. (PMID: 22206904)
J Clin Invest. 2021 Apr 1;131(7):. (PMID: 33792560)
Front Immunol. 2018 Nov 20;9:2692. (PMID: 30515169)
Methods Mol Biol. 2019;1884:119-130. (PMID: 30465198)
Front Immunol. 2021 Apr 13;12:653605. (PMID: 33927722)
Front Cell Dev Biol. 2019 Mar 11;7:28. (PMID: 30915331)
JCI Insight. 2017 Dec 7;2(23):. (PMID: 29212954)
J Immunol. 2014 Jun 15;192(12):5451-8. (PMID: 24907378)
Cell Metab. 2012 May 2;15(5):606-14. (PMID: 22560213)
N Engl J Med. 2018 Feb 1;378(5):439-448. (PMID: 29385370)
J Transl Med. 2021 Dec 7;19(1):499. (PMID: 34876185)
J Clin Invest. 2005 Jun;115(6):1616-26. (PMID: 15931392)
Cell. 2018 Nov 29;175(6):1701-1715.e16. (PMID: 30449622)
Nature. 2019 Jul;571(7764):270-274. (PMID: 31207604)
Nat Cancer. 2023 Jul;4(7):968-983. (PMID: 37248395)
Front Immunol. 2022 Apr 13;13:876339. (PMID: 35493513)
Immunity. 2016 Sep 20;45(3):701-703. (PMID: 27653602)
Genes Dev. 2005 Jan 15;19(2):224-33. (PMID: 15655112)
Immunooncol Technol. 2022 Jun 22;15:100090. (PMID: 35965844)
Cancer Immunol Immunother. 2019 Jul;68(7):1195-1209. (PMID: 31177329)
J Lipid Res. 2016 Jun;57(6):943-54. (PMID: 27080715)
Sci Immunol. 2021 Mar 26;6(57):. (PMID: 33771887)
Sci Transl Med. 2014 Feb 19;6(224):224ra25. (PMID: 24553386)
Nat Commun. 2021 May 14;12(1):2804. (PMID: 33990571)
Neurobiol Aging. 2023 Mar;123:75-82. (PMID: 36638683)
Blood Cancer J. 2021 Apr 6;11(4):69. (PMID: 33824268)
Cancer Immunol Res. 2021 Aug;9(8):856-861. (PMID: 34344697)
Lancet. 2020 Sep 19;396(10254):839-852. (PMID: 32888407)
Blood. 2017 Jun 22;129(25):3322-3331. (PMID: 28408462)
J Clin Oncol. 2011 Mar 1;29(7):917-24. (PMID: 21282551)
Nat Immunol. 2013 Mar;14(3):238-45. (PMID: 23354485)
J Exp Med. 1977 Sep 1;146(3):698-709. (PMID: 302304)
Lancet. 2015 Feb 7;385(9967):517-528. (PMID: 25319501)
Blood. 2024 Feb 1;143(5):456-472. (PMID: 37976448)
Nat Med. 2018 Jun;24(6):731-738. (PMID: 29808005)
Leukemia. 2016 Feb;30(2):492-500. (PMID: 26369987)
Cell Rep Med. 2023 Sep 19;4(9):101161. (PMID: 37595589)
Exp Biol Med (Maywood). 2012 Jul;237(7):748-57. (PMID: 22859740)
J Immunol. 2022 Jan 1;208(1):155-168. (PMID: 34872976)
Cancer Immunol Res. 2021 Dec;9(12):1425-1438. (PMID: 34686489)
Cell Death Discov. 2017 May 29;3:17031. (PMID: 28580175)
Cancer Immunol Res. 2019 May;7(5):759-772. (PMID: 30890531)
Front Immunol. 2022 Aug 23;13:879608. (PMID: 36081506)
Blood Cancer Discov. 2022 Jan;3(1):66-81. (PMID: 35019853)
J Clin Oncol. 2022 Jun 1;40(16):1741-1754. (PMID: 35104158)
Nat Commun. 2017 Dec 12;8(1):2068. (PMID: 29233977)
Front Immunol. 2023 May 15;14:1188049. (PMID: 37256141)
Cell Mol Immunol. 2021 Jul;18(7):1761-1771. (PMID: 32055005)
Int J Mol Sci. 2023 Mar 16;24(6):. (PMID: 36982764)
Sci Transl Med. 2015 Mar 25;7(280):280ps7. (PMID: 25810311)
Nat Med. 2019 Jul;25(7):1064-1072. (PMID: 31235963)
Immunity. 2016 Feb 16;44(2):380-90. (PMID: 26885860)
J Clin Invest. 2016 Jun 1;126(6):2123-38. (PMID: 27111235)
Nature. 2022 Apr;604(7906):563-570. (PMID: 35418687)
Blood. 2009 Jul 16;114(3):535-46. (PMID: 19451549)
Nat Med. 2018 Jan;24(1):20-28. (PMID: 29155426)
J Immunol. 1996 May 15;156(10):3678-86. (PMID: 8621902)
Front Immunol. 2021 Jun 03;12:666231. (PMID: 34149701)
Nat Rev Immunol. 2022 Feb;22(2):85-96. (PMID: 34002066)
Blood Adv. 2020 Oct 13;4(19):4898-4911. (PMID: 33035333)
Lymphokine Res. 1986 Fall;5(4):289-99. (PMID: 2946903)
Sci Immunol. 2020 Nov 6;5(53):. (PMID: 33158974)
Cytokine. 2015 Aug;74(2):213-8. (PMID: 25922276)
Immunity. 2016 Jun 21;44(6):1299-311. (PMID: 27234056)
J Immunol. 1999 Jun 1;162(11):6671-80. (PMID: 10352285)
Science. 2013 Oct 11;342(6155):1242454. (PMID: 24115444)
Blood. 2015 Aug 20;126(8):983-92. (PMID: 26056165)
Blood Cancer Discov. 2022 Mar 01;3(2):136-153. (PMID: 35015685)
J Clin Invest. 2020 Oct 1;130(10):5425-5443. (PMID: 32925169)
Mol Cell Biol. 2013 Jun;33(11):2302-14. (PMID: 23530063)
Blood. 2014 Jun 12;123(24):3750-9. (PMID: 24782509)
Cancer Res. 1983 Aug;43(8):3507-10. (PMID: 6861123)
Cancers (Basel). 2022 Nov 04;14(21):. (PMID: 36358860)
Cytokine. 2022 Dec;160:156049. (PMID: 36201890)
Nature. 2009 Jul 2;460(7251):103-7. (PMID: 19494812)
Nat Immunol. 2013 Dec;14(12):1294-301. (PMID: 24162776)
Nat Rev Immunol. 2020 Mar;20(3):173-185. (PMID: 31676858)
Haematologica. 2023 Feb 01;108(2):457-471. (PMID: 35950535)
Immunity. 1998 Oct;9(4):575-85. (PMID: 9806643)
J Immunother Cancer. 2023 Mar;11(3):. (PMID: 36914208)
Immunity. 2014 Jul 17;41(1):75-88. (PMID: 25001241)
Immunol Rev. 2008 Apr;222:129-44. (PMID: 18363998)
Clin Cancer Res. 2019 Mar 1;25(5):1486-1493. (PMID: 30518633)
Mol Cell Biol. 2007 Apr;27(8):2952-66. (PMID: 17283040)
Proc Natl Acad Sci U S A. 2002 Oct 15;99(21):13735-40. (PMID: 12374858)
Immunol Rev. 2012 Sep;249(1):27-42. (PMID: 22889213)
Cancer Res. 2011 May 15;71(10):3516-27. (PMID: 21558388)
Blood. 2016 Mar 10;127(10):1361-70. (PMID: 26660684)
Nat Rev Clin Oncol. 2023 Jun;20(6):359-371. (PMID: 37055515)
J Clin Invest. 2016 Nov 1;126(11):4262-4272. (PMID: 27760047)
Methods Mol Biol. 2019;1978:13-26. (PMID: 31119654)
Science. 2006 Oct 6;314(5796):126-9. (PMID: 16946036)
J Immunother Cancer. 2017 Mar 21;5:26. (PMID: 28331616)
Immunol Rev. 2012 Sep;249(1):14-26. (PMID: 22889212)
Cold Spring Harb Protoc. 2016 Feb 01;2016(2):pdb.prot090704. (PMID: 26832688)
J Exp Med. 2002 Aug 19;196(4):447-57. (PMID: 12186837)
Blood. 2018 Nov 1;132(18):1899-1910. (PMID: 30209120)
EBioMedicine. 2021 Dec;74:103734. (PMID: 34875457)
Immunity. 2019 Aug 20;51(2):285-297.e5. (PMID: 31272808)
Leukemia. 2018 May;32(5):1157-1167. (PMID: 29479065)
J Immunother Cancer. 2023 Jan;11(1):. (PMID: 36593069)
Mol Ther. 2020 Nov 4;28(11):2379-2393. (PMID: 32735774)
Trends Pharmacol Sci. 2023 Jul;44(7):442-456. (PMID: 37248103)
J Clin Invest. 2013 Oct;123(10):4479-88. (PMID: 24091329)
N Engl J Med. 2017 Dec 28;377(26):2531-2544. (PMID: 29226797)
Int J Mol Sci. 2019 Mar 14;20(6):. (PMID: 30875739)
N Engl J Med. 2024 Feb 15;390(7):584-586. (PMID: 38265704)
Blood Adv. 2020 Nov 10;4(21):5414-5424. (PMID: 33147337)
Virchows Arch. 2019 Apr;474(4):449-461. (PMID: 30470934)
Nat Med. 2018 Jun;24(6):739-748. (PMID: 29808007)
Immunity. 2011 Dec 23;35(6):871-82. (PMID: 22195744)
Proc Natl Acad Sci U S A. 2021 Sep 14;118(37):. (PMID: 34507993)
Mol Ther Oncolytics. 2018 Nov 06;11:127-137. (PMID: 30581986)
Nat Commun. 2020 Jul 3;11(1):3360. (PMID: 32620763)
Sci Immunol. 2020 Jul 3;5(49):. (PMID: 32620560)
معلومات مُعتمدة: CA260909 U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI); CA223389 U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI); CA086913 U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI); P30CA046934 U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI); AI149187 U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases (NIAID); AI148434 U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases (NIAID); 634956 Hyundai Motor Group | Hyundai Motor America | Hyundai Hope On Wheels (Hope On Wheels)
المشرفين على المادة: 0 (Mitochondrial Proteins)
9006-59-1 (Ovalbumin)
تواريخ الأحداث: Date Created: 20240524 Date Completed: 20240524 Latest Revision: 20240611
رمز التحديث: 20240612
مُعرف محوري في PubMed: PMC11126743
DOI: 10.1038/s41467-024-48653-y
PMID: 38789421
قاعدة البيانات: MEDLINE
الوصف
تدمد:2041-1723
DOI:10.1038/s41467-024-48653-y