ATM activity in T cells is critical for immune surveillance of lymphoma in vivo.
Journal
Leukemia
ISSN: 1476-5551
Titre abrégé: Leukemia
Pays: England
ID NLM: 8704895
Informations de publication
Date de publication:
03 2020
03 2020
Historique:
received:
13
05
2019
accepted:
24
10
2019
revised:
25
09
2019
pubmed:
7
11
2019
medline:
25
8
2020
entrez:
7
11
2019
Statut:
ppublish
Résumé
The proximal DNA damage response kinase ATM is frequently inactivated in human malignancies. Germline mutations in the ATM gene cause Ataxia-telangiectasia (A-T), characterized by cerebellar ataxia and cancer predisposition. Whether ATM deficiency impacts on tumor initiation or also on the maintenance of the malignant state is unclear. Here, we show that Atm reactivation in initially Atm-deficient B- and T cell lymphomas induces tumor regression. We further find a reduced T cell abundance in B cell lymphomas from Atm-defective mice and A-T patients. Using T cell-specific Atm-knockout models, as well as allogeneic transplantation experiments, we pinpoint impaired immune surveillance as a contributor to cancer predisposition and development. Moreover, we demonstrate that Atm-deficient T cells display impaired proliferation capacity upon stimulation, due to replication stress. Altogether, our data indicate that T cell-specific restoration of ATM activity or allogeneic hematopoietic stem cell transplantation may prevent lymphomagenesis in A-T patients.
Identifiants
pubmed: 31690822
doi: 10.1038/s41375-019-0618-2
pii: 10.1038/s41375-019-0618-2
doi:
Substances chimiques
Etoposide
6PLQ3CP4P3
Ataxia Telangiectasia Mutated Proteins
EC 2.7.11.1
Atm protein, mouse
EC 2.7.11.1
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
771-786Références
Jackson SP, Bartek J. The DNA-damage response in human biology and disease. Nature. 2009;461:1071–8.
doi: 10.1038/nature08467
pubmed: 2906700
pmcid: 2906700
Matsuoka S, Ballif BA, Smogorzewska A, McDonald ER 3rd, Hurov KE, Luo J, et al. ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage. Science. 2007;316:1160–6.
doi: 10.1126/science.1140321
Shiloh Y, Ziv Y. The ATM protein kinase: regulating the cellular response to genotoxic stress, and more. Nat Rev Mol Cell Biol. 2013;14:197–210.
doi: 10.1038/nrm3546
Jachimowicz RD, Beleggia F, Isensee J, Velpula BB, Goergens J, Bustos MA, et al. UBQLN4 represses homologous recombination and is overexpressed in aggressive tumors. Cell. 2019;176:505–19.e22. https://doi.org/10.1016/j.cell.2018.11.024 . Epub 3 Jan 2019.
Shiloh Y, Lederman HM. Ataxia-telangiectasia (A-T): an emerging dimension of premature ageing. Ageing Res Rev. 2017;33:76–88. https://doi.org/10.1016/j.arr.2016.05.002 . Epub 12 May 2016.
Savitsky K, Bar-Shira A, Gilad S, Rotman G, Ziv Y, Vanagaite L, et al. A single ataxia telangiectasia gene with a product similar to PI-3 kinase. Science. 1995;268:1749–53.
doi: 10.1126/science.7792600
Kandoth C, McLellan MD, Vandin F, Ye K, Niu B, Lu C, et al. Mutational landscape and significance across 12 major cancer types. Nature. 2013;502:333–9.
doi: 10.1038/nature12634
pubmed: 3927368
pmcid: 3927368
Zack TI, Schumacher SE, Carter SL, Cherniack AD, Saksena G, Tabak B, et al. Pan-cancer patterns of somatic copy number alteration. Nat Genet. 2013;45:1134–40.
doi: 10.1038/ng.2760
pubmed: 3966983
pmcid: 3966983
Alexandrov LB, Nik-Zainal S, Wedge DC, Aparicio SA, Behjati S, Biankin AV, et al. Signatures of mutational processes in human cancer. Nature. 2013;500:415–21.
doi: 10.1038/nature12477
Perkhofer L, Schmitt A, Romero Carrasco MC, Ihle M, Hampp S, Ruess DA, et al. ATM deficiency generating genomic instability sensitizes pancreatic ductal adenocarcinoma cells to therapy-induced DNA damage. Cancer Res. 2017;77:5576–90. https://doi.org/10.1158/0008-5472.CAN-17-0634 . Epub 8 Aug 2017.
Schmitt A, Knittel G, Welcker D, Yang TP, George J, Nowak M, et al. ATM deficiency is associated with sensitivity to PARP1 and ATR inhibitors in lung adenocarcinoma. Cancer Res. 2017;77:3040–56. https://doi.org/10.1158/0008-5472.CAN-16-3398 . Epub 31 Mar 2017.
Ventura A, Kirsch DG, McLaughlin ME, Tuveson DA, Grimm J, Lintault L, et al. Restoration of p53 function leads to tumour regression in vivo. Nature. 2007;445:661–5.
doi: 10.1038/nature05541
Xue W, Zender L, Miething C, Dickins RA, Hernando E, Krizhanovsky V, et al. Senescence and tumour clearance is triggered by p53 restoration in murine liver carcinomas. Nature. 2007;445:656–60.
doi: 10.1038/nature05529
pubmed: 17251933
pmcid: 17251933
Sakai W, Swisher EM, Karlan BY, Agarwal MK, Higgins J, Friedman C, et al. Secondary mutations as a mechanism of cisplatin resistance in BRCA2-mutated cancers. Nature. 2008;451:1116–20.
doi: 10.1038/nature06633
pubmed: 2577037
pmcid: 2577037
Edwards SL, Brough R, Lord CJ, Natrajan R, Vatcheva R, Levine DA, et al. Resistance to therapy caused by intragenic deletion in BRCA2. Nature. 2008;451:1111–5.
doi: 10.1038/nature06548
pubmed: 18264088
pmcid: 18264088
Siliciano JD, Canman CE, Taya Y, Sakaguchi K, Appella E, Kastan MB. DNA damage induces phosphorylation of the amino terminus of p53. Genes Dev. 1997;11:3471–81.
doi: 10.1101/gad.11.24.3471
pubmed: 316806
pmcid: 316806
Reinhardt HC, Yaffe MB. Phospho-Ser/Thr-binding domains: navigating the cell cycle and DNA damage response. Nat Rev Mol Cell Biol. 2013;14:563–80.
doi: 10.1038/nrm3640
Wang X, Andreassen PR, D’Andrea AD. Functional interaction of monoubiquitinated FANCD2 and BRCA2/FANCD1 in chromatin. Mol Cell Biol. 2004;24:5850–62.
doi: 10.1128/MCB.24.13.5850-5862.2004
pubmed: 480901
pmcid: 480901
Bahassi EM, Ovesen JL, Riesenberg AL, Bernstein WZ, Hasty PE, Stambrook PJ. The checkpoint kinases Chk1 and Chk2 regulate the functional associations between hBRCA2 and Rad51 in response to DNA damage. Oncogene. 2008;27:3977–85.
doi: 10.1038/onc.2008.17
Nowak-Wegrzyn A, Crawford TO, Winkelstein JA, Carson KA, Lederman HM. Immunodeficiency and infections in ataxia-telangiectasia. J Pediatr. 2004;144:505–11.
doi: 10.1016/j.jpeds.2003.12.046
Genik PC, Bielefeldt-Ohmann H, Liu X, Story MD, Ding L, Bush JM, et al. Strain background determines lymphoma incidence in Atm knockout mice. Neoplasia. 2014;16:129–36.
doi: 10.1593/neo.131980
pubmed: 3978393
pmcid: 3978393
Barlow C, Hirotsune S, Paylor R, Liyanage M, Eckhaus M, Collins F, et al. Atm-deficient mice: a paradigm of ataxia telangiectasia. Cell. 1996;86:159–71.
doi: 10.1016/S0092-8674(00)80086-0
Xu Y, Ashley T, Brainerd EE, Bronson RT, Meyn MS, Baltimore D. Targeted disruption of ATM leads to growth retardation, chromosomal fragmentation during meiosis, immune defects, and thymic lymphoma. Genes Dev. 1996;10:2411–22.
doi: 10.1101/gad.10.19.2411
Gage BM, Alroy D, Shin CY, Ponomareva ON, Dhar S, Sharma GG, et al. Spontaneously immortalized cell lines obtained from adult Atm null mice retain sensitivity to ionizing radiation and exhibit a mutational pattern suggestive of oxidative stress. Oncogene. 2001;20:4291–7.
doi: 10.1038/sj.onc.1204509
Shiloh Y, Tabor E, Becker Y. Abnormal response of ataxia-telangiectasia cells to agents that break the deoxyribose moiety of DNA via a targeted free radical mechanism. Carcinogenesis. 1983;4:1317–22.
doi: 10.1093/carcin/4.10.1317
Borghesani PR, Alt FW, Bottaro A, Davidson L, Aksoy S, Rathbun GA, et al. Abnormal development of Purkinje cells and lymphocytes in Atm mutant mice. Proc Natl Acad Sci USA. 2000;97:3336–41.
doi: 10.1073/pnas.97.7.3336
Li J, Chen J, Vinters HV, Gatti RA, Herrup K. Stable brain ATM message and residual kinase-active ATM protein in ataxia-telangiectasia. J Neurosci. 2011;313:7568–77.
doi: 10.1523/JNEUROSCI.0778-11.2011
Crawford TO. Ataxia telangiectasia. Semin Pediatr Neurol. 1998;5:287–94.
doi: 10.1016/S1071-9091(98)80007-7
Bottini AR, Gatti RA, Wirenfeldt M, Vinters HV. Heterotopic Purkinje cells in ataxia-telangiectasia. Neuropathol: Off J Jpn Soc Neuropathol. 2012;32:23–29.
doi: 10.1111/j.1440-1789.2011.01210.x
Elson A, Wang Y, Daugherty CJ, Morton CC, Zhou F, Campos-Torres J, et al. Pleiotropic defects in ataxia-telangiectasia protein-deficient mice. Proc Natl Acad Sci USA. 1996;93:13084–9.
doi: 10.1073/pnas.93.23.13084
Utermohlen O, Schulze-Garg C, Warnecke G, Gugel R, Lohler J, Deppert W. Simian virus 40 large-T-antigen-specific rejection of mKSA tumor cells in BALB/c mice is critically dependent on both strictly tumor-associated, tumor-specific CD8(+) cytotoxic T lymphocytes and CD4(+) T helper cells. J Virol. 2001;75:10593–602.
doi: 10.1128/JVI.75.22.10593-10602.2001
pubmed: 114641
pmcid: 114641
Patrussi L, Baldari CT. Intracellular mediators of CXCR4-dependent signaling in T cells. Immunol Lett. 2008;115:75–82.
doi: 10.1016/j.imlet.2007.10.012
Asselin-Labat ML, David M, Biola-Vidamment A, Lecoeuche D, Zennaro MC, Bertoglio J, et al. GILZ, a new target for the transcription factor FoxO3, protects T lymphocytes from interleukin-2 withdrawal-induced apoptosis. Blood. 2004;104:215–23.
doi: 10.1182/blood-2003-12-4295
pubmed: 15031210
pmcid: 15031210
Ashburner M, Ball CA, Blake JA, Botstein D, Butler H, Cherry JM, et al. Gene ontology: tool for the unification of biology. The Gene Ontology Consortium. Nat Genet. 2000;25:25–29.
doi: 10.1038/75556
pubmed: 3037419
pmcid: 3037419
The Gene Ontology C. Expansion of the Gene Ontology knowledgebase and resources. Nucleic Acids Res. 2017;45(D1):D331–D338.
doi: 10.1093/nar/gkw1108
Akbar AN, Henson SM. Are senescence and exhaustion intertwined or unrelated processes that compromise immunity? Nat Rev Immunol. 2011;11:289–95.
doi: 10.1038/nri2959
Subramanian A, Tamayo P, Mootha VK, Mukherjee S, Ebert BL, Gillette MA, et al. Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. Proc Natl Acad Sci USA. 2005;102:15545–50.
doi: 10.1073/pnas.0506580102
pubmed: 16199517
pmcid: 16199517
Wherry EJ. T cell exhaustion. Nat Immunol. 2011;12:492–9.
doi: 10.1038/ni.2035
Fathman CG, Lineberry NB. Molecular mechanisms of CD4+ T-cell anergy. Nat Rev Immunol. 2007;7:599–609.
doi: 10.1038/nri2131
Her J, Ray C, Altshuler J, Zheng H, Bunting SF 53BP1 mediates ATR-Chk1 signaling and protects replication forks under conditions of replication stress. Mol Cell Biol. 2018;38:e00472–17.
Toledo LI, Altmeyer M, Rask MB, Lukas C, Larsen DH, Povlsen LK, et al. ATR prohibits replication catastrophe by preventing global exhaustion of RPA. Cell. 2013;155:1088–103.
doi: 10.1016/j.cell.2013.10.043
Zou L, Elledge SJ. Sensing DNA damage through ATRIP recognition of RPA-ssDNA complexes. Science. 2003;300:1542–8.
doi: 10.1126/science.1083430
Kotsantis P, Petermann E, Boulton SJ. Mechanisms of oncogene-induced replication stress: jigsaw falling into place. Cancer Discov. 2018;8:537–55.
doi: 10.1158/2159-8290.CD-17-1461
pubmed: 5935233
pmcid: 5935233
Bienemann K, Burkhardt B, Modlich S, Meyer U, Moricke A, Bienemann K, et al. Promising therapy results for lymphoid malignancies in children with chromosomal breakage syndromes (Ataxia teleangiectasia or Nijmegen-breakage syndrome): a retrospective survey. Br J Haematol. 2011;155:468–76.
doi: 10.1111/j.1365-2141.2011.08863.x
Pietzner J, Baer PC, Duecker RP, Merscher MB, Satzger-Prodinger C, Bechmann I, et al. Bone marrow transplantation improves the outcome of Atm-deficient mice through the migration of ATM-competent cells. Hum Mol Genet. 2013;22:493–507.
doi: 10.1093/hmg/dds448
Ussowicz M, Musial J, Duszenko E, Haus O, Kalwak K. Long-term survival after allogeneic-matched sibling PBSC transplantation with conditioning consisting of low-dose busilvex and fludarabine in a 3-year-old boy with ataxia-telangiectasia syndrome and ALL. Bone Marrow Transpl. 2013;48:740–1.
doi: 10.1038/bmt.2012.207
Ribeil JA, Hacein-Bey-Abina S, Payen E, Magnani A, Semeraro M, Magrin E, et al. Gene therapy in a patient with sickle cell disease. N Engl J Med. 2017;376:848–55.
doi: 10.1056/NEJMoa1609677
Knittel G, Liedgens P, Korovkina D, Seeger JM, Al-Baldawi Y, Al-Maarri M, et al. B cell-specific conditional expression of Myd88p.L252P leads to the development of diffuse large B cell lymphoma in mice. Blood. 2016;127:2732–41. https://doi.org/10.1182/blood-2015-11-684183 . Epub 5 Apr 2016.
Knittel G, Rehkamper T, Korovkina D, Liedgens P, Fritz C, Torgovnick A, et al. Two mouse models reveal an actionable PARP1 dependence in aggressive chronic lymphocytic leukemia. Nat Commun. 2017;8:153.
doi: 10.1038/s41467-017-00210-6
pubmed: 5532225
pmcid: 5532225