CD52 and OXPHOS-potential targets in ibrutinib-treated mantle cell lymphoma.
Journal
Cell death discovery
ISSN: 2058-7716
Titre abrégé: Cell Death Discov
Pays: United States
ID NLM: 101665035
Informations de publication
Date de publication:
31 Dec 2022
31 Dec 2022
Historique:
received:
25
11
2022
accepted:
16
12
2022
revised:
15
12
2022
entrez:
31
12
2022
pubmed:
1
1
2023
medline:
1
1
2023
Statut:
epublish
Résumé
Altered features of tumor cells acquired across therapy can result in the survival of treatment-resistant clones that may cause minimal residual disease (MRD). Despite the efficacy of ibrutinib in treating relapsed/refractory mantle cell lymphoma, the obstacle of residual cells contributes to relapses of this mature B-cell neoplasm, and the disease remains incurable. RNA-seq analysis of an ibrutinib-sensitive mantle cell lymphoma cell line following ibrutinib incubation of up to 4 d, corroborated our previously postulated resistance mechanism of a metabolic switch to reliance on oxidative phosphorylation (OXPHOS) in surviving cells. Besides, we had shown that treatment-persisting cells were characterized by increased CD52 expression. Therefore, we hypothesized that combining ibrutinib with another agent targeting these potential escape mechanisms could minimize the risk of survival of ibrutinib-resistant cells. Concomitant use of ibrutinib with OXPHOS-inhibitor IACS-010759 increased toxicity compared to ibrutinib alone. Targeting CD52 was even more efficient, as addition of CD52 mAb in combination with human serum following ibrutinib pretreatment led to rapid complement-dependent-cytotoxicity in an ibrutinib-sensitive cell line. In primary mantle cell lymphoma cells, a higher toxic effect with CD52 mAb was obtained, when cells were pretreated with ibrutinib, but only in an ibrutinib-sensitive cohort. Given the challenge of treating multi-resistant mantle cell lymphoma patients, this work highlights the potential use of anti-CD52 therapy as consolidation after ibrutinib treatment in patients who responded to the BTK inhibitor to achieve MRD negativity and prolong progression-free survival.
Identifiants
pubmed: 36587029
doi: 10.1038/s41420-022-01289-7
pii: 10.1038/s41420-022-01289-7
pmc: PMC9805448
doi:
Types de publication
Journal Article
Langues
eng
Pagination
505Informations de copyright
© 2023. The Author(s).
Références
Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri S, Stein H, et al. WHO classification of tumours of haematopoietic and lymphoid tissues. Lyon: International Agency for Research on Cancer; 2017.
Welzel N, Le T, Marculescu R, Mitterbauer G, Chott A, Pott C, et al. Templated nucleotide addition and immunoglobulin JH-gene utilization in t(11;14) junctions: implications for the mechanism of translocation and the origin of mantle cell lymphoma. Cancer Res. 2001;61:1629–36.
Morgane C, Coralie D, Aurore T, Stéphanie S, Adrien G, Amélie T, et al. Minimal residual disease monitoring by 8-color flow cytometry in mantle cell lymphoma: an EU-MCL and LYSA study. Haematologica. 2016;101:336–45.
doi: 10.3324/haematol.2015.134957
Hoster E, Pott C. Minimal residual disease in mantle cell lymphoma: insights into biology and impact on treatment. Hematol Am Soc Hematol Educ Program. 2016;2016:437–45.
doi: 10.1182/asheducation-2016.1.437
Hermine O, Hoster E, Walewski J, Bosly A, Stilgenbauer S, Thieblemont C, et al. Addition of high-dose cytarabine to immunochemotherapy before autologous stem-cell transplantation in patients aged 65 years or younger with mantle cell lymphoma (MCL Younger): a randomised, open-label, phase 3 trial of the European Mantle Cell Lymphoma Network. Lancet. 2016;388:565–75.
doi: 10.1016/S0140-6736(16)00739-X
Saba NS, Liu D, Herman SE, Underbayev C, Tian X, Behrend D, et al. Pathogenic role of B-cell receptor signaling and canonical NF-κB activation in mantle cell lymphoma. Blood. 2016;128:82–92.
doi: 10.1182/blood-2015-11-681460
Fuhr V, Vafadarnejad E, Dietrich O, Arampatzi P, Riedel A, Saliba AE, et al. Time-Resolved scRNA-Seq Tracks the Adaptation of a Sensitive MCL Cell Line to Ibrutinib Treatment. Int J Mol Sci. 2021;22:2276.
doi: 10.3390/ijms22052276
Faubert B, Solmonson A, DeBerardinis RJ. Metabolic reprogramming and cancer progression. Science. 2020;368:eaaw5473.
doi: 10.1126/science.aaw5473
Hanahan D. Hallmarks of cancer: new dimensions. Cancer Discov. 2022;12:31–46.
doi: 10.1158/2159-8290.CD-21-1059
Böttcher M, Baur R, Stoll A, Mackensen A, Mougiakakos D. Linking immunoevasion and metabolic reprogramming in B-cell-derived lymphomas. Front Oncol. 2020;10:594782.
doi: 10.3389/fonc.2020.594782
Warburg O, Wind F, Negelein E. The metabolism of tumors in the body. J Gen Physiol. 1927;8:519–30.
doi: 10.1085/jgp.8.6.519
Kuntz EM, Baquero P, Michie AM, Dunn K, Tardito S, Holyoake TL, et al. Targeting mitochondrial oxidative phosphorylation eradicates therapy-resistant chronic myeloid leukemia stem cells. Nat Med. 2017;23:1234–40.
doi: 10.1038/nm.4399
Lee KM, Giltnane JM, Balko JM, Schwarz LJ, Guerrero-Zotano AL, Hutchinson KE, et al. MYC and MCL1 cooperatively promote chemotherapy-resistant breast cancer stem cells via regulation of mitochondrial oxidative phosphorylation. Cell Metab. 2017;26:633–47.e7.
doi: 10.1016/j.cmet.2017.09.009
Lee S, Lee JS, Seo J, Lee SH, Kang JH, Song J, et al. Targeting mitochondrial oxidative phosphorylation abrogated irinotecan resistance in NSCLC. Sci Rep. 2018;8:15707.
doi: 10.1038/s41598-018-33667-6
Farge T, Saland E, de Toni F, Aroua N, Hosseini M, Perry R, et al. Chemotherapy-resistant human acute myeloid leukemia cells are not enriched for leukemic stem cells but require oxidative metabolism. Cancer Discov. 2017;7:716–35.
doi: 10.1158/2159-8290.CD-16-0441
Vazquez F, Lim JH, Chim H, Bhalla K, Girnun G, Pierce K, et al. PGC1α expression defines a subset of human melanoma tumors with increased mitochondrial capacity and resistance to oxidative stress. Cancer Cell. 2013;23:287–301.
doi: 10.1016/j.ccr.2012.11.020
Bosc C, Selak MA, Sarry JE. Resistance is futile: targeting mitochondrial energetics and metabolism to overcome drug resistance in cancer treatment. Cell Metab. 2017;26:705–7.
doi: 10.1016/j.cmet.2017.10.013
Lee SC, Shestov AA, Guo L, Zhang Q, Roman JC, Liu X, et al. Metabolic detection of Bruton’s tyrosine kinase inhibition in mantle cell lymphoma cells. Mol Cancer Res. 2019;17:1365–77.
doi: 10.1158/1541-7786.MCR-18-0256
Zhang L, Yao Y, Zhang S, Liu Y, Guo H, Ahmed M, et al. Metabolic reprogramming toward oxidative phosphorylation identifies a therapeutic target for mantle cell lymphoma. Sci Transl Med. 2019;11:eaau1167.
doi: 10.1126/scitranslmed.aau1167
Molina JR, Sun Y, Protopopova M, Gera S, Bandi M, Bristow C, et al. An inhibitor of oxidative phosphorylation exploits cancer vulnerability. Nat Med. 2018;24:1036–46.
doi: 10.1038/s41591-018-0052-4
Bello C, Sotomayor EM. Monoclonal antibodies for B-cell lymphomas: rituximab and beyond. Hematology. 2007;2007:233–42.
doi: 10.1182/asheducation-2007.1.233
Treumann A, Lifely MR, Schneider P, Ferguson MA. Primary structure of CD52. J Biol Chem. 1995;270:6088–99.
doi: 10.1074/jbc.270.11.6088
Rao SP, Sancho J, Campos-Rivera J, Boutin PM, Severy PB, Weeden T, et al. Human peripheral blood mononuclear cells exhibit heterogeneous CD52 expression levels and show differential sensitivity to alemtuzumab mediated cytolysis. PLoS ONE. 2012;7:e39416.
doi: 10.1371/journal.pone.0039416
Klabusay M, Sukova V, Coupek P, Brychtova Y, Mayer J. Different levels of CD52 antigen expression evaluated by quantitative fluorescence cytometry are detected on B-lymphocytes, CD 34+ cells and tumor cells of patients with chronic B-cell lymphoproliferative diseases. Cytom B Clin Cytom. 2007;72:363–70.
doi: 10.1002/cyto.b.20181
Rowan WC, Hale G, Tite JP, Brett SJ. Cross-linking of the CAMPATH-1 antigen (CD52) triggers activation of normal human T lymphocytes. Int Immunol. 1995;7:69–77.
doi: 10.1093/intimm/7.1.69
Watanabe T, Masuyama J-i, Sohma Y, Inazawa H, Horie K, Kojima K, et al. CD52 is a novel costimulatory molecule for induction of CD4+ regulatory T cells. Clin Immunol. 2006;120:247–59.
doi: 10.1016/j.clim.2006.05.006
Masuyama J-i, Yoshio T, Suzuki K, Kitagawa S, Iwamoto M, Kamimura T, et al. Characterization of the 4C8 antigen involved in transendothelial migration of CD26hi T cells after tight adhesion to human umbilical vein endothelial cell monolayers. J Exp Med. 1999;189:979–90.
doi: 10.1084/jem.189.6.979
Kirchhoff C, Schröter S. New insights into the origin, structure and role of CD52: a major component of the mammalian sperm glycocalyx. Cells Tissues Organs. 2001;168:93–104.
doi: 10.1159/000016810
Rudnik M, Rolski F, Jordan S, Mertelj T, Stellato M, Distler O, et al. Regulation of monocyte adhesion and type I interferon signaling by CD52 in patients with systemic sclerosis. Arthritis Rheumatol. 2021;73:1720–30.
doi: 10.1002/art.41737
Bhamidipati K, Silberstein JL, Chaichian Y, Baker MC, Lanz TV, Zia A, et al. CD52 is elevated on B cells of SLE patients and regulates B cell function. Front Immunol. 2020;11:626820.
doi: 10.3389/fimmu.2020.626820
Cohen JA, Coles AJ, Arnold DL, Confavreux C, Fox EJ, Hartung H-P, et al. Alemtuzumab versus interferon beta 1a as first-line treatment for patients with relapsing-remitting multiple sclerosis: a randomised controlled phase 3 trial. Lancet. 2012;380:1819–28.
doi: 10.1016/S0140-6736(12)61769-3
Coles AJ, Twyman CL, Arnold DL, Cohen JA, Confavreux C, Fox EJ, et al. Alemtuzumab for patients with relapsing multiple sclerosis after disease-modifying therapy: a randomised controlled phase 3 trial. Lancet. 2012;380:1829–39.
doi: 10.1016/S0140-6736(12)61768-1
Keating MJ, Flinn I, Jain V, Binet J-L, Hillmen P, Byrd J, et al. Therapeutic role of alemtuzumab (Campath-1H) in patients who have failed fludarabine: results of a large international study. Blood. 2002;99:3554–61.
doi: 10.1182/blood.V99.10.3554
Nückel H, Frey UH, Röth A, Dührsen U, Siffert W. Alemtuzumab induces enhanced apoptosis in vitro in B-cells from patients with chronic lymphocytic leukemia by antibody-dependent cellular cytotoxicity. Eur J Pharm. 2005;514:217–24.
doi: 10.1016/j.ejphar.2005.03.024
Zent CS, Secreto CR, LaPlant BR, Bone ND, Call TG, Shanafelt TD, et al. Direct and complement dependent cytotoxicity in CLL cells from patients with high-risk early-intermediate stage chronic lymphocytic leukemia (CLL) treated with alemtuzumab and rituximab. Leuk Res. 2008;32:1849–56.
doi: 10.1016/j.leukres.2008.05.014
Stanglmaier M, Reis S, Hallek M. Rituximab and alemtuzumab induce a nonclassic, caspase-independent apoptotic pathway in B-lymphoid cell lines and in chronic lymphocytic leukemia cells. Ann Hematol. 2004;83:634–45.
doi: 10.1007/s00277-004-0917-0
Zent CS, Chen JB, Kurten RC, Kaushal GP, Marie Lacy H, Schichman SA. Alemtuzumab (CAMPATH 1H) does not kill chronic lymphocytic leukemia cells in serum free medium. Leuk Res. 2004;28:495–507.
doi: 10.1016/j.leukres.2003.09.011
Wang H, Zhang W, Yang J, Zhou K. The resistance mechanisms and treatment strategies of BTK inhibitors in B-cell lymphoma. Hematol Oncol. 2021;39:605–15.
doi: 10.1002/hon.2933
Wang ML, Jurczak W, Jerkeman M, Trotman J, Zinzani PL, Belada D, et al. Ibrutinib plus bendamustine and rituximab in untreated Mantle-cell lymphoma. N Engl J Med. 2022;386:2482–94.
doi: 10.1056/NEJMoa2201817
Tam CS, Anderson MA, Pott C, Agarwal R, Handunnetti S, Hicks RJ, et al. Ibrutinib plus venetoclax for the treatment of Mantle-cell lymphoma. N Engl J Med. 2018;378:1211–23.
doi: 10.1056/NEJMoa1715519
Le Gouill S, Morschhauser F, Chiron D, Bouabdallah K, Cartron G, Casasnovas O, et al. Ibrutinib, obinutuzumab, and venetoclax in relapsed and untreated patients with mantle cell lymphoma: a phase 1/2 trial. Blood. 2021;137:877–87.
doi: 10.1182/blood.2020008727
Chiron D, Di Liberto M, Martin P, Huang X, Sharman J, Blecua P, et al. Cell-cycle reprogramming for PI3K inhibition overrides a relapse-specific C481S BTK mutation revealed by longitudinal functional genomics in mantle cell lymphoma. Cancer Discov. 2014;4:1022–35.
doi: 10.1158/2159-8290.CD-14-0098
Rauert-Wunderlich H, Rudelius M, Berberich I, Rosenwald A. CD40L mediated alternative NFκB-signaling induces resistance to BCR-inhibitors in patients with mantle cell lymphoma. Cell Death Dis. 2018;9:86.
doi: 10.1038/s41419-017-0157-6
Chiron D, Bellanger C, Papin A, Tessoulin B, Dousset C, Maiga S, et al. Rational targeted therapies to overcome microenvironment-dependent expansion of mantle cell lymphoma. Blood. 2016;128:2808–18.
doi: 10.1182/blood-2016-06-720490
Vander Heiden MG, Cantley LC, Thompson CB. Understanding the Warburg effect: the metabolic requirements of cell proliferation. Science. 2009;324:1029–33.
doi: 10.1126/science.1160809
Ackermann T, Tardito S. Cell culture medium formulation and its implications in cancer metabolism. Trends Cancer. 2019;5:329–32.
doi: 10.1016/j.trecan.2019.05.004
Muir A, Vander, Heiden MG. The nutrient environment affects therapy. Science. 2018;360:962–3.
doi: 10.1126/science.aar5986
Sica V, Bravo-San Pedro JM, Stoll G, Kroemer G. Oxidative phosphorylation as a potential therapeutic target for cancer therapy. Int J Cancer. 2020;146:10–7.
doi: 10.1002/ijc.32616
Sharif-Askari B, Doyon D, Paliouras M, Aloyz R. Bruton’s tyrosine kinase is at the crossroads of metabolic adaptation in primary malignant human lymphocytes. Sci Rep. 2019;9:11069.
doi: 10.1038/s41598-019-47305-2
Wu W, Wang W, Franzen CA, Guo H, Lee J, Li Y, et al. Inhibition of B-cell receptor signaling disrupts cell adhesion in mantle cell lymphoma via RAC2. Blood Adv. 2021;5:185–97.
doi: 10.1182/bloodadvances.2020001665
Chang BY, Francesco M, De Rooij MF, Magadala P, Steggerda SM, Huang MM, et al. Egress of CD19(+)CD5(+) cells into peripheral blood following treatment with the Bruton tyrosine kinase inhibitor ibrutinib in mantle cell lymphoma patients. Blood. 2013;122:2412–24.
doi: 10.1182/blood-2013-02-482125
Wang ML, Rule S, Martin P, Goy A, Auer R, Kahl BS, et al. Targeting BTK with ibrutinib in relapsed or refractory mantle-cell lymphoma. N Engl J Med. 2013;369:507–16.
doi: 10.1056/NEJMoa1306220
McCulloch R, Lewis D, Crosbie N, Eyre TA, Bolam S, Arasaretnam A, et al. Ibrutinib for mantle cell lymphoma at first relapse: a United Kingdom real-world analysis of outcomes in 211 patients. Br J Haematol. 2021;193:290–8.
doi: 10.1111/bjh.17363
Hayashi K, Nagasaki E, Kan S, Ito M, Kamata Y, Homma S, et al. Gemcitabine enhances rituximab-mediated complement-dependent cytotoxicity to B cell lymphoma by CD20 upregulation. Cancer Sci. 2016;107:682–9.
doi: 10.1111/cas.12918
Winqvist M, Palma M, Heimersson K, Mellstedt H, Österborg A, Lundin J. Dual targeting of Bruton tyrosine kinase and CD52 induces minimal residual disease-negativity in the bone marrow of poor-prognosis chronic lymphocytic leukaemia patients but is associated with opportunistic infections - Results from a phase I study. Br J Haematol. 2018;182:590–4.
doi: 10.1111/bjh.14836
Skoetz N, Bauer K, Elter T, Monsef I, Roloff V, Hallek M, et al. Alemtuzumab for patients with chronic lymphocytic leukaemia. Cochrane Database Syst Rev. 2012;2012:Cd008078.
Yu J, Song Y, Tian W. How to select IgG subclasses in developing anti-tumor therapeutic antibodies. J Hematol Oncol. 2020;13:45.
doi: 10.1186/s13045-020-00876-4
Hu Y, Turner MJ, Shields J, Gale MS, Hutto E, Roberts BL, et al. Investigation of the mechanism of action of alemtuzumab in a human CD52 transgenic mouse model. Immunology. 2009;128:260–70.
doi: 10.1111/j.1365-2567.2009.03115.x
Rauert-Wunderlich H, Rudelius M, Ott G, Rosenwald A. Targeting protein kinase C in mantle cell lymphoma. Br J Haematol. 2016;173:394–403.
doi: 10.1111/bjh.13973
Martin M. Cutadapt removes adapter sequences from high-throughput sequencing reads. EMBnet.journal. 2011;17:10–12.
doi: 10.14806/ej.17.1.200
Dobin A, Davis CA, Schlesinger F, Drenkow J, Zaleski C, Jha S, et al. STAR: ultrafast universal RNA-seq aligner. Bioinformatics. 2013;29:15–21.
doi: 10.1093/bioinformatics/bts635
Liao Y, Smyth GK, Shi W. featureCounts: an efficient general purpose program for assigning sequence reads to genomic features. Bioinformatics. 2014;30:923–30.
doi: 10.1093/bioinformatics/btt656
Love MI, Huber W, Anders S. Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol. 2014;15:550.
doi: 10.1186/s13059-014-0550-8
Yu G, Wang LG, Han Y, He QY. clusterProfiler: an R package for comparing biological themes among gene clusters. Omics. 2012;16:284–7.
doi: 10.1089/omi.2011.0118