دورية أكاديمية
أعرض في EDS

Leukemia-intrinsic determinants of CAR-T response revealed by iterative in vivo genome-wide CRISPR screening.

التفاصيل البيبلوغرافية
العنوان: Leukemia-intrinsic determinants of CAR-T response revealed by iterative in vivo genome-wide CRISPR screening.
المؤلفون: Ramos A; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA.; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA, USA., Koch CE; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA.; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA, USA., Liu-Lupo Y; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA.; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA, USA., Hellinger RD; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA., Kyung T; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA.; Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA., Abbott KL; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA.; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA, USA., Fröse J; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA., Goulet D; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA., Gordon KS; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA.; Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA., Eidell KP; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA., Leclerc P; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA., Whittaker CA; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA., Larson RC; Cellular Immunotherapy Program, Cancer Center, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA.; Immunology Program, Harvard Medical School, Boston, MA, USA., Muscato AJ; Center for Cancer Research, Massachusetts General Hospital, Charlestown, MA, USA.; Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, Massachusetts, 02142, USA., Yates KB; Center for Cancer Research, Massachusetts General Hospital, Charlestown, MA, USA.; Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, Massachusetts, 02142, USA., Dubrot J; Center for Cancer Research, Massachusetts General Hospital, Charlestown, MA, USA.; Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, Massachusetts, 02142, USA.; Solid Tumors Program, Division of Oncology, Center for Applied Medical Research (CIMA), University of Navarra, Pamplona, Spain., Doench JG; Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, Massachusetts, 02142, USA., Regev A; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA, USA.; Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, Massachusetts, 02142, USA.; Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA.; Howard Hughes Medical Institute, Chevy Chase, MD, USA., Vander Heiden MG; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA.; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA, USA.; Dana-Farber Cancer Institute, Boston, MA, USA., Maus MV; Cellular Immunotherapy Program, Cancer Center, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA.; Immunology Program, Harvard Medical School, Boston, MA, USA.; Center for Cancer Research, Massachusetts General Hospital, Charlestown, MA, USA.; Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, Massachusetts, 02142, USA.; Ragon Institute of MIT, MGH, and Harvard, Cambridge, MA, USA., Manguso RT; Immunology Program, Harvard Medical School, Boston, MA, USA.; Center for Cancer Research, Massachusetts General Hospital, Charlestown, MA, USA.; Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, Massachusetts, 02142, USA., Birnbaum ME; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA.; Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA., Hemann MT; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA. hemann@mit.edu.; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA, USA. hemann@mit.edu.
المصدر: Nature communications [Nat Commun] 2023 Dec 05; Vol. 14 (1), pp. 8048. Date of Electronic Publication: 2023 Dec 05.
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: Receptors, Chimeric Antigen* , Precursor B-Cell Lymphoblastic Leukemia-Lymphoma*/genetics , Precursor B-Cell Lymphoblastic Leukemia-Lymphoma*/therapy , Leukemia* , Burkitt Lymphoma*, Humans ; Animals ; Mice ; RNA, Guide, CRISPR-Cas Systems ; Immunotherapy, Adoptive ; T-Lymphocytes ; Tumor Microenvironment
مستخلص: CAR-T therapy is a promising, novel treatment modality for B-cell malignancies and yet many patients relapse through a variety of means, including loss of CAR-T cells and antigen escape. To investigate leukemia-intrinsic CAR-T resistance mechanisms, we performed genome-wide CRISPR-Cas9 loss-of-function screens in an immunocompetent murine model of B-cell acute lymphoblastic leukemia (B-ALL) utilizing a modular guide RNA library. We identified IFNγR/JAK/STAT signaling and components of antigen processing and presentation pathway as key mediators of resistance to CAR-T therapy in vivo; intriguingly, loss of this pathway yielded the opposite effect in vitro (sensitized leukemia to CAR-T cells). Transcriptional characterization of this model demonstrated upregulation of these pathways in tumors relapsed after CAR-T treatment, and functional studies showed a surprising role for natural killer (NK) cells in engaging this resistance program. Finally, examination of data from B-ALL patients treated with CAR-T revealed an association between poor outcomes and increased expression of JAK/STAT and MHC-I in leukemia cells. Overall, our data identify an unexpected mechanism of resistance to CAR-T therapy in which tumor cell interaction with the in vivo tumor microenvironment, including NK cells, induces expression of an adaptive, therapy-induced, T-cell resistance program in tumor cells.
(© 2023. The Author(s).)
References: Nat Commun. 2016 Jul 27;7:12320. (PMID: 27460500)
Nature. 2017 Mar 2;543(7643):113-117. (PMID: 28225754)
Nat Rev Genet. 2018 Feb;19(2):67-80. (PMID: 29199283)
Nat Methods. 2017 Apr;14(4):417-419. (PMID: 28263959)
Ann Oncol. 2018 Jan 1;29(1):84-91. (PMID: 29228097)
N Engl J Med. 2020 Apr 2;382(14):1331-1342. (PMID: 32242358)
Cancer Discov. 2015 Dec;5(12):1282-95. (PMID: 26516065)
Cancer Discov. 2021 Sep;11(9):2248-2265. (PMID: 33837065)
N Engl J Med. 2018 Feb 1;378(5):439-448. (PMID: 29385370)
Nat Cancer. 2023 Jul;4(7):968-983. (PMID: 37248395)
J Exp Med. 1993 Aug 1;178(2):567-77. (PMID: 8101861)
Sci Immunol. 2021 Mar 26;6(57):. (PMID: 33771887)
Eur J Immunol. 1998 Jan;28(1):264-76. (PMID: 9485206)
Front Immunol. 2019 Nov 12;10:2664. (PMID: 31798590)
N Engl J Med. 2016 Dec 29;375(26):2561-9. (PMID: 28029927)
Blood. 2020 Feb 27;135(9):597-609. (PMID: 31830245)
Blood. 2010 Nov 11;116(19):3875-86. (PMID: 20631379)
Cancer Discov. 2018 Oct;8(10):1219-1226. (PMID: 30135176)
Mol Ther. 2017 Jan 4;25(1):285-295. (PMID: 28129122)
Proc Natl Acad Sci U S A. 2006 Apr 25;103(17):6688-93. (PMID: 16618932)
Cell. 2018 Dec 13;175(7):1731-1743.e13. (PMID: 30503213)
Nature. 1998 Feb 19;391(6669):795-9. (PMID: 9486650)
N Engl J Med. 2018 Jul 5;379(1):64-73. (PMID: 29972754)
Lancet. 2015 Feb 7;385(9967):517-528. (PMID: 25319501)
Blood. 2019 Apr 11;133(15):1652-1663. (PMID: 30728140)
Hum Gene Ther. 2012 Oct;23(10):1043-53. (PMID: 22780919)
Blood. 2021 May 13;137(19):2621-2633. (PMID: 33512407)
Haematologica. 2016 May;101(5):626-33. (PMID: 26721894)
J Clin Invest. 2002 Nov;110(10):1515-23. (PMID: 12438449)
Nat Med. 2018 Oct;24(10):1504-1506. (PMID: 30275569)
Front Immunol. 2017 Apr 06;8:391. (PMID: 28428785)
Nat Rev Cancer. 2021 Mar;21(3):145-161. (PMID: 33483715)
J Clin Invest. 2022 Sep 1;132(17):. (PMID: 35881486)
Nature. 2022 Apr;604(7906):563-570. (PMID: 35418687)
Genes Dev. 2007 Sep 15;21(18):2283-7. (PMID: 17761812)
Science. 2018 Mar 23;359(6382):1361-1365. (PMID: 29567707)
Nat Med. 2018 Jan;24(1):20-28. (PMID: 29155426)
Cancer Cell. 2017 Oct 9;32(4):411-426.e11. (PMID: 28966034)
Nat Biotechnol. 2014 Dec;32(12):1262-7. (PMID: 25184501)
Genes Dev. 2015 Mar 1;29(5):483-8. (PMID: 25737277)
Hum Gene Ther. 2003 Aug 10;14(12):1155-68. (PMID: 12908967)
Nature. 2017 Jul 27;547(7664):413-418. (PMID: 28723893)
F1000Res. 2015 Dec 30;4:1521. (PMID: 26925227)
Nat Immunol. 2022 Oct;23(10):1495-1506. (PMID: 36151395)
Blood Adv. 2022 Nov 22;6(22):5844-5856. (PMID: 35728062)
Nat Rev Clin Oncol. 2019 May;16(5):277-278. (PMID: 30824813)
Immunity. 2016 Jun 21;44(6):1444-54. (PMID: 27332733)
Trends Immunol. 2003 Apr;24(4):162-4. (PMID: 12697440)
J Immunother Cancer. 2019 Oct 17;7(1):263. (PMID: 31623687)
Nat Rev Clin Oncol. 2019 Jun;16(6):372-385. (PMID: 30837712)
Cell. 2016 Dec 1;167(6):1540-1554.e12. (PMID: 27912061)
N Engl J Med. 2019 Jan 3;380(1):45-56. (PMID: 30501490)
Blood Cancer Discov. 2022 Mar 01;3(2):136-153. (PMID: 35015685)
N Engl J Med. 2017 Dec 28;377(26):2545-2554. (PMID: 29226764)
Nat Med. 2018 May;24(5):563-571. (PMID: 29713085)
PLoS One. 2013 Apr 09;8(4):e61338. (PMID: 23585892)
Cell. 2015 Dec 3;163(6):1515-26. (PMID: 26627737)
Front Immunol. 2022 Jul 14;13:927265. (PMID: 35911672)
Immunity. 2006 Aug;25(2):331-42. (PMID: 16901727)
Clin Cancer Res. 2020 Nov 1;26(21):5549-5556. (PMID: 32409305)
Sci Transl Med. 2017 Jul 19;9(399):. (PMID: 28724573)
Nature. 2020 Oct;586(7827):120-126. (PMID: 32968282)
J Biol Chem. 2022 Oct;298(10):102484. (PMID: 36108743)
Cell. 2019 Aug 8;178(4):933-948.e14. (PMID: 31398344)
Cell. 2018 Dec 13;175(7):1744-1755.e15. (PMID: 30503208)
Cancer Discov. 2020 Apr;10(4):552-567. (PMID: 32001516)
J Clin Invest. 2016 Nov 1;126(11):4262-4272. (PMID: 27760047)
Science. 2016 Apr 8;352(6282):189-96. (PMID: 27124452)
Cell. 2021 Dec 9;184(25):6119-6137.e26. (PMID: 34890551)
Blood Adv. 2018 Jun 12;2(11):1229-1242. (PMID: 29853524)
N Engl J Med. 2018 Feb 1;378(5):449-459. (PMID: 29385376)
N Engl J Med. 2017 Dec 28;377(26):2531-2544. (PMID: 29226797)
J Clin Invest. 2019 Mar 12;129(5):2123-2132. (PMID: 30860496)
N Engl J Med. 2013 Apr 18;368(16):1509-1518. (PMID: 23527958)
معلومات مُعتمدة: R21 AI151827 United States AI NIAID NIH HHS; P30 CA014051 United States CA NCI NIH HHS; R35 CA242379 United States CA NCI NIH HHS; T32 GM144273 United States GM NIGMS NIH HHS; T32 AI007529 United States AI NIAID NIH HHS; R01 CA226898 United States CA NCI NIH HHS; T32 GM007753 United States GM NIGMS NIH HHS; R01 CA233477 United States CA NCI NIH HHS
المشرفين على المادة: 0 (Receptors, Chimeric Antigen)
0 (RNA, Guide, CRISPR-Cas Systems)
تواريخ الأحداث: Date Created: 20231205 Date Completed: 20231207 Latest Revision: 20240623
رمز التحديث: 20240623
مُعرف محوري في PubMed: PMC10698189
DOI: 10.1038/s41467-023-43790-2
PMID: 38052854
قاعدة البيانات: MEDLINE
الوصف
تدمد:2041-1723
DOI:10.1038/s41467-023-43790-2