دورية أكاديمية
أعرض في EDS

Expression of modified FcγRI enables myeloid cells to elicit robust tumor-specific cytotoxicity.

التفاصيل البيبلوغرافية
العنوان: Expression of modified FcγRI enables myeloid cells to elicit robust tumor-specific cytotoxicity.
المؤلفون: Farhat-Younis L; Department of Pathology, School of Medicine, Tel Aviv University, Tel Aviv, Israel., Na M; Department of Pathology, School of Medicine, Tel Aviv University, Tel Aviv, Israel., Zarfin A; Department of Pathology, School of Medicine, Tel Aviv University, Tel Aviv, Israel., Khateeb A; Department of Pathology, School of Medicine, Tel Aviv University, Tel Aviv, Israel., Santana-Magal N; Department of Pathology, School of Medicine, Tel Aviv University, Tel Aviv, Israel., Richter A; Department of Pathology, School of Medicine, Tel Aviv University, Tel Aviv, Israel., Gutwillig A; Department of Pathology, School of Medicine, Tel Aviv University, Tel Aviv, Israel., Rasoulouniriana D; Department of Pathology, School of Medicine, Tel Aviv University, Tel Aviv, Israel., Gleiberman A; Department of Pathology, School of Medicine, Tel Aviv University, Tel Aviv, Israel., Beck L; Department of Human Molecular Genetics and Biochemistry, Tel Aviv University, Tel Aviv, Israel., Giger T; Department of Molecular Cell Biology, Weizmann Institute, Rehovot, Israel., Ashkenazi A; Department of Cell and Developmental Biology, School of Medicine, Tel Aviv University, Tel Aviv, Israel., Barzel A; Department of Biochemistry Molecular Biology, George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv, Israel., Rider P; Department of Pathology, School of Medicine, Tel Aviv University, Tel Aviv, Israel., Carmi Y; Department of Pathology, School of Medicine, Tel Aviv University, Tel Aviv, Israel.
المصدر: ELife [Elife] 2024 Jun 17; Vol. 12. Date of Electronic Publication: 2024 Jun 17.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: eLife Sciences Publications, Ltd Country of Publication: England NLM ID: 101579614 Publication Model: Electronic Cited Medium: Internet ISSN: 2050-084X (Electronic) Linking ISSN: 2050084X NLM ISO Abbreviation: Elife Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Cambridge, UK : eLife Sciences Publications, Ltd., 2012-
مواضيع طبية MeSH: Receptors, IgG*/metabolism , Receptors, IgG*/immunology , Myeloid Cells*/immunology , Myeloid Cells*/metabolism, Animals ; Mice ; Mice, Inbred C57BL ; Cell Line, Tumor ; Cytotoxicity, Immunologic ; Immunoglobulin M/metabolism ; Immunoglobulin M/immunology ; Signal Transduction ; Macrophages/immunology ; Macrophages/metabolism ; Neoplasms/immunology
مستخلص: Despite the central role of T cells in tumor immunity, attempts to harness their cytotoxic capacity as a therapy have met limited efficacy, partially as a result of the suppressive microenvironment which limits their migration and activation. In contrast, myeloid cells massively infiltrate tumors and are well adapted to survive these harsh conditions. While they are equipped with cell-killing abilities, they often adopt an immunosuppressive phenotype upon migration to tumors. Therefore, the questions of how to modify their activation programming against cancer, and what signaling cascades should be activated in myeloid cells to elicit their cytotoxicity have remained unclear. Here, we found that activation of IgM-induced signaling in murine myeloid cells results in secretion of lytic granules and massive tumor cell death. These findings open venues for designing novel immunotherapy by equipping monocytes with chimeric receptors that target tumor antigens and consequently, signal through IgM receptor. Nonetheless, we found that myeloid cells do not express the antibody-derived portion used to recognize the tumor antigen due to the induction of an ER stress response. To overcome this limitation, we designed chimeric receptors that are based on the high-affinity FcγRI for IgG. Incubation of macrophages expressing these receptors along with tumor-binding IgG induced massive tumor cell killing and secretion of reactive oxygen species and Granzyme B. Overall, this work highlights the challenges involved in genetically reprogramming the signaling in myeloid cells and provides a framework for endowing myeloid cells with antigen-specific cytotoxicity.
Competing Interests: LF, MN, AZ, AK, NS, AR, AG, AG, LB, TG, AA, AB No competing interests declared, DR This paper was funded by Gilboa Therapeutics where Diana Rasoulouniriana is a shareholder, PR This paper was funded by Gilboa Therapeutics where Peleg Rider is a shareholder, YC This paper was funded by Gilboa Therapeutics where Yaron Carmi is a shareholder
(© 2023, Farhat-Younis et al.)
التعليقات: Erratum in: Elife. 2024 Jul 02;13:e101165. doi: 10.7554/eLife.101165. (PMID: 38953289)
References: Clin Cancer Res. 2007 Dec 1;13(23):7119-25. (PMID: 18056192)
Science. 2011 Mar 25;331(6024):1612-6. (PMID: 21436454)
Nature. 2017 May 25;545(7655):495-499. (PMID: 28514441)
Sci Transl Med. 2011 Aug 10;3(95):95ra73. (PMID: 21832238)
Nat Rev Clin Oncol. 2017 Jul;14(7):399-416. (PMID: 28117416)
Br J Cancer. 2020 Oct;123(9):1353-1355. (PMID: 32830198)
Elife. 2018 Jun 04;7:. (PMID: 29862966)
Blood. 2009 Jul 16;114(3):535-46. (PMID: 19451549)
Nat Biotechnol. 2020 Aug;38(8):947-953. (PMID: 32361713)
Cancer Immunol Res. 2013 Aug;1(2):99-111. (PMID: 24459675)
Mol Ther. 2015 Aug;23(8):1391-1400. (PMID: 25997427)
Carbohydr Polym. 2020 Nov 1;247:116715. (PMID: 32829842)
Am J Transl Res. 2012;4(4):376-89. (PMID: 23145206)
Nature. 2015 May 7;521(7550):99-104. (PMID: 25924063)
Nat Commun. 2020 Jan 30;11(1):603. (PMID: 32001676)
Cancer Immunol Immunother. 2014 Sep;63(9):969-75. (PMID: 24943274)
Front Immunol. 2019 Jul 12;10:1563. (PMID: 31354719)
Front Immunol. 2021 May 07;12:642285. (PMID: 34025653)
Front Immunol. 2021 Nov 24;12:783305. (PMID: 34899748)
Annu Rev Pharmacol Toxicol. 2016;56:59-83. (PMID: 26738472)
Science. 2013 Jan 18;339(6117):286-91. (PMID: 23329041)
Nat Cancer. 2021 Jan;2(1):18-33. (PMID: 35121890)
Cancer Cell. 2012 Mar 20;21(3):309-22. (PMID: 22439926)
Science. 2019 Jul 12;365(6449):162-168. (PMID: 31296767)
Mol Carcinog. 2020 Jul;59(7):862-870. (PMID: 32386086)
Annu Rev Med. 2017 Jan 14;68:139-152. (PMID: 27860544)
Front Immunol. 2018 Jan 23;9:37. (PMID: 29410669)
JCI Insight. 2016 Nov 3;1(18):e89020. (PMID: 27812544)
Immunity. 2018 Apr 17;48(4):812-830.e14. (PMID: 29628290)
Methods Enzymol. 2011;490:71-92. (PMID: 21266244)
Nat Rev Cancer. 2012 Mar 15;12(4):298-306. (PMID: 22419253)
Proc Natl Acad Sci U S A. 2010 Nov 16;107(46):19985-90. (PMID: 21045130)
Science. 2015 Apr 3;348(6230):74-80. (PMID: 25838376)
Nat Rev Immunol. 2020 Nov;20(11):651-668. (PMID: 32433532)
Immunity. 2019 Jul 16;51(1):27-41. (PMID: 31315034)
Sci Transl Med. 2017 May 10;9(389):. (PMID: 28490665)
Nat Rev Cancer. 2020 Nov;20(11):662-680. (PMID: 32753728)
J Exp Med. 2019 Jun 3;216(6):1244-1254. (PMID: 31068379)
Nat Rev Clin Oncol. 2020 Mar;17(3):147-167. (PMID: 31848460)
J Biol Chem. 2016 May 27;291(22):11504-17. (PMID: 27022031)
Nat Biomed Eng. 2018 Aug;2(8):578-588. (PMID: 31015631)
Cancer Immunol Immunother. 2015 Jan;64(1):123-30. (PMID: 25488419)
Cell. 2010 Mar 19;140(6):883-99. (PMID: 20303878)
Elife. 2020 May 05;9:. (PMID: 32367803)
Nat Immunol. 2013 Oct;14(10):1014-22. (PMID: 24048123)
Curr Opin Immunol. 2010 Apr;22(2):231-7. (PMID: 20144856)
Gene Ther. 2006 Apr;13(7):602-10. (PMID: 16397508)
فهرسة مساهمة: Keywords: ER stress; chimeric antigen receptor; immunology; immunotherapy; inflammation; mouse; myeloid cells
المشرفين على المادة: 0 (Receptors, IgG)
0 (Immunoglobulin M)
تواريخ الأحداث: Date Created: 20240617 Date Completed: 20240617 Latest Revision: 20240702
رمز التحديث: 20240702
مُعرف محوري في PubMed: PMC11182644
DOI: 10.7554/eLife.91999
PMID: 38885133
قاعدة البيانات: MEDLINE
الوصف
تدمد:2050-084X
DOI:10.7554/eLife.91999