Bone marrow dendritic cells support the survival of chronic lymphocytic leukemia cells in a CD84 dependent manner.
Animals
Apoptosis
Bone Marrow
/ immunology
Cell Proliferation
Dendritic Cells
/ immunology
Female
Humans
Leukemia, Lymphocytic, Chronic, B-Cell
/ immunology
Mice
Mice, Transgenic
Prognosis
Signaling Lymphocytic Activation Molecule Family
/ metabolism
Tumor Cells, Cultured
Tumor Microenvironment
/ immunology
Journal
Oncogene
ISSN: 1476-5594
Titre abrégé: Oncogene
Pays: England
ID NLM: 8711562
Informations de publication
Date de publication:
02 2020
02 2020
Historique:
received:
18
04
2019
accepted:
13
11
2019
revised:
11
11
2019
pubmed:
28
11
2019
medline:
25
11
2020
entrez:
28
11
2019
Statut:
ppublish
Résumé
Chronic lymphocytic leukemia (CLL) is a malignancy of mature B lymphocytes. The microenvironment of the CLL cells is a vital element in the regulation of the survival of these malignant cells. CLL cell longevity is dependent on external signals, originating from cells in their microenvironment including secreted and surface-bound factors. Dendritic cells (DCs) play an important part in tumor microenvironment, but their role in the CLL bone marrow (BM) niche has not been studied. We show here that CLL cells induce accumulation of bone marrow dendritic cells (BMDCs). Depletion of this population attenuates disease expansion. Our results show that the support of the microenvironment is partly dependent on CD84, a cell surface molecule belonging to the Signaling Lymphocyte Activating Molecule (SLAM) family of immunoreceptors. Our results suggest a novel therapeutic strategy whereby eliminating BMDCs or blocking the CD84 expressed on these cells may reduce the tumor load.
Identifiants
pubmed: 31772329
doi: 10.1038/s41388-019-1121-y
pii: 10.1038/s41388-019-1121-y
doi:
Substances chimiques
CD84 protein, human
0
Signaling Lymphocytic Activation Molecule Family
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1997-2008Références
Klein U, Dalla-Favera R. New insights into the pathogenesis of chronic lymphocytic leukemia. Semin Cancer Biol. 2010;20:377–83.
pubmed: 21029776
doi: 10.1016/j.semcancer.2010.10.012
Montserrat E, Moreno C. Chronic lymphocytic leukaemia: a short overview. Ann Oncol. 2008;19(Suppl 7):vii320–25.
pubmed: 18790975
doi: 10.1093/annonc/mdn460
Caligaris-Cappio F, Hamblin TJ. B-cell chronic lymphocytic leukemia: a bird of a different feather. J Clin Oncol. 1999;17:399–408.
pubmed: 10458259
doi: 10.1200/JCO.1999.17.1.399
Kipps TJ. Chronic lymphocytic leukemia. Curr Opin Hematol. 1998;5:244–53.
pubmed: 9747630
doi: 10.1097/00062752-199807000-00003
Gale RP, Caligaris-Cappio F, Dighiero G, Keating M, Montserrat E, Rai K. Recent progress in chronic lymphocytic leukemia. International Workshop on chronic Lymphocytic Leukemia. Leukemia. 1994;8:1610–4.
pubmed: 7522296
Binet JL, Leporrier M, Dighiero G, Charron D, Dathis P, Vaugier G, et al. Clinical staging system for chronic lymphocytic-leukemia—prognostic significance. Cancer. 1977;40:855–64.
pubmed: 890666
doi: 10.1002/1097-0142(197708)40:2<855::AID-CNCR2820400239>3.0.CO;2-1
Rai KR, Sawitsky A, Cronkite EP, Chanana AD, Levy RN, Pasternack BS. Clinical staging of chronic lymphocytic leukemia. Blood. 1975;46:219–34.
pubmed: 1139039
doi: 10.1182/blood.V46.2.219.219
Nicholas NS, Apollonio B, Ramsay AG. Tumor microenvironment (TME)-driven immune suppression in B cell malignancy. Biochim Biophys Acta. 2016;1863:471–82.
pubmed: 26554850
doi: 10.1016/j.bbamcr.2015.11.003
Bichi R, Shinton SA, Martin ES, Koval A, Calin GA, Cesari R, et al. Human chronic lymphocytic leukemia modeled in mouse by targeted TCL1 expression. Proc Natl Acad Sci USA. 2002;99:6955–60.
pubmed: 12011454
doi: 10.1073/pnas.102181599
pmcid: 124510
Burger JA. No cell is an island unto itself: the stromal microenvironment in chronic lymphocytic leukemia. Leuk Res. 2007;31:887–8.
pubmed: 17234265
doi: 10.1016/j.leukres.2006.12.004
Ramsay AD, Rodriguez-Justo M. Chronic lymphocytic leukaemia-the role of the microenvironment pathogenesis and therapy. Br J Haematol. 2013;162:15–24.
pubmed: 23617880
doi: 10.1111/bjh.12344
Lagneaux L, Delforge A, Bron D, De Bruyn C, Stryckmans P. Chronic lymphocytic leukemic B cells but not normal B cells are rescued from apoptosis by contact with normal bone marrow stromal cells. Blood. 1998;91:2387–96.
pubmed: 9516138
doi: 10.1182/blood.V91.7.2387
de Visser KE, Eichten A, Coussens LM. Paradoxical roles of the immune system during cancer development. Nat Rev Cancer. 2006;6:24–37.
pubmed: 16397525
doi: 10.1038/nrc1782
Sapoznikov A, Pewzner-Jung Y, Kalchenko V, Krauthgamer R, Shachar I, Jung S. Perivascular clusters of dendritic cells provide critical survival signals to B cells in bone marrow niches. Nat Immunol. 2008;9:388–95.
pubmed: 18311142
doi: 10.1038/ni1571
Karthaus N, Torensma R, Tel J. Deciphering the message broadcast by tumor-infiltrating dendritic cells. Am J Pathol. 2012;181:733–42.
pubmed: 22796439
doi: 10.1016/j.ajpath.2012.05.012
Calpe S, Wang NH, Romero X, Berger SB, Lanyi A, Engel P, et al. The SLAM and SAP gene families control innate and adaptive immune responses. Adv Immunol. 2008;97:177–250.
pubmed: 18501771
doi: 10.1016/S0065-2776(08)00004-7
Martin M, Romero X, de la Fuente MA, Tovar V, Zapater N, Esplugues E, et al. CD84 functions as a homophilic adhesion molecule and enhances IFN-gamma secretion: adhesion is mediated by Ig-like domain 1. J Immunol. 2001;167:3668–76.
pubmed: 11564780
doi: 10.4049/jimmunol.167.7.3668
Romero X, Zapater N, Calvo M, Kalko SG, de la Fuente MA, Tovar V, et al. CD229 (Ly9) lymphocyte cell surface receptor interacts homophilically through its N-terminal domain and relocalizes to the immunological synapse. J Immunol. 2005;174:7033–42.
pubmed: 15905546
doi: 10.4049/jimmunol.174.11.7033
Yan QR, Malashkevich VN, Fedorov A, Fedorov E, Cao E, Lary JW, et al. Structure of CD84 provides insight into SLAM family function. Proc Natl Acad Sci USA. 2007;104:10583–8.
pubmed: 17563375
doi: 10.1073/pnas.0703893104
pmcid: 1965556
Binsky-Ehrenreich I, Marom A, Sobotta MC, Shvidel L, Berrebi A, Hazan-Halevy I, et al. CD84 is a survival receptor for CLL cells. Oncogene. 2014;33:1006–16.
pubmed: 23435417
doi: 10.1038/onc.2013.31
Marom A, Barak AF, Kramer MP, Lewinsky H, Binsky-Ehrenreich I, Cohen S, et al. CD84 mediates CLL-microenvironment interactions. Oncogene. 2017;36:628–38.
pubmed: 27452524
doi: 10.1038/onc.2016.238
Lewinsky H, Barak AF, Huber V, Kramer MP, Radomir L, Sever L, et al. CD84 regulates PD-1/PD-L1 expression and function in chronic lymphocytic leukemia. J Clin Investig. 2018;128:5465–78.
pubmed: 30277471
doi: 10.1172/JCI96610
pmcid: 6264738
Hofbauer JP, Heyder C, Denk U, Kocher T, Holler C, Trapin D, et al. Development of CLL in the TCL1 transgenic mouse model is associated with severe skewing of the T-cell compartment homologous to human CLL. Leukemia. 2011;25:1452–8.
pubmed: 21606964
doi: 10.1038/leu.2011.111
Saulep-Easton D, Vincent FB, Le Page M, Wei A, Ting SB, Croce CM, et al. Cytokine-driven loss of plasmacytoid dendritic cell function in chronic lymphocytic leukemia. Leukemia. 2014;28:2005–15.
pubmed: 24721775
pmcid: 4100939
doi: 10.1038/leu.2014.105
Mildner A, Jung S. Development and function of dendritic cell subsets. Immunity. 2014;40:642–56.
pubmed: 24837101
doi: 10.1016/j.immuni.2014.04.016
Ginhoux F, Jung S. Monocytes and macrophages: developmental pathways and tissue homeostasis. Nat Rev Immunol. 2014;14:392–404.
pubmed: 24854589
doi: 10.1038/nri3671
Serbina NV, Pamer EG. Monocyte emigration from bone marrow during bacterial infection requires signals mediated by chemokine receptor CCR2. Nat Immunol. 2006;7:311–7.
pubmed: 16462739
doi: 10.1038/ni1309
Jung S, Aliberti J, Graemmel P, Sunshine MJ, Kreutzberg GW, Sher A, et al. Analysis of fractalkine receptor CX(3)CR1 function by targeted deletion and green fluorescent protein reporter gene insertion. Mol Cell Biol. 2000;20:4106–14.
pubmed: 10805752
pmcid: 85780
doi: 10.1128/MCB.20.11.4106-4114.2000
Cabanas C, Sanchez-Madrid F. CD11c (leukocyte integrin CR4 alpha subunit). J Biol Regul Homeost Agents. 1999;13:134–6.
pubmed: 10503738
Yang J, Zhang L, Yu C, Yang XF, Wang H. Monocyte and macrophage differentiation: circulation inflammatory monocyte as biomarker for inflammatory diseases. Biomark Res. 2014;2:1.
pubmed: 24398220
pmcid: 3892095
doi: 10.1186/2050-7771-2-1
Galletti G, Scielzo C, Barbaglio F, Rodriguez TV, Riba M, Lazarevic D, et al. Targeting macrophages sensitizes chronic lymphocytic leukemia to apoptosis and inhibits disease progression. Cell Rep. 2016;14:1748–60.
pubmed: 26876171
doi: 10.1016/j.celrep.2016.01.042
Birnberg T, Bar-On L, Sapoznikov A, Caton ML, Cervantes-Barragan L, Makia D, et al. Lack of conventional dendritic cells is compatible with normal development and T cell homeostasis, but causes myeloid proliferative syndrome. Immunity. 2008;29:986–97.
pubmed: 19062318
doi: 10.1016/j.immuni.2008.10.012
Zlotnikov-Klionsky Y, Nathansohn-Levi B, Shezen E, Rosen C, Kagan S, Bar-On L, et al. Perforin-positive dendritic cells exhibit an immuno-regulatory role in metabolic syndrome and autoimmunity. Immunity. 2015;43:776–87.
pubmed: 26384546
doi: 10.1016/j.immuni.2015.08.015
Jung S, Unutmaz D, Wong P, Sano G, De los Santos K, Sparwasser T, et al. In vivo depletion of CD11c(+) dendritic cells abrogates priming of CD8(+) T cells by exogenous cell-associated antigens. Immunity. 2002;17:211–20.
pubmed: 12196292
pmcid: 3689299
doi: 10.1016/S1074-7613(02)00365-5
Sapoznikov A, Jung S. Probing in vivo dendritic cell functions by conditional cell ablation. Immunol Cell Biol. 2008;86:409–15.
pubmed: 18414431
doi: 10.1038/icb.2008.23
Hanna BS, McClanahan F, Yazdanparast H, Zaborsky N, Kalter V, Rossner PM, et al. Depletion of CLL-associated patrolling monocytes and macrophages controls disease development and repairs immune dysfunction in vivo. Leukemia. 2016;30:570–9.
pubmed: 26522085
doi: 10.1038/leu.2015.305
Ghiringhelli F, Puig PE, Roux S, Parcellier A, Schmitt E, Solary E, et al. Tumor cells convert immature myeloid dendritic cells into TGF-beta-secreting cells inducing CD4+CD25+ regulatory T cell proliferation. J Exp Med. 2005;202:919–29.
pubmed: 16186184
pmcid: 2213166
doi: 10.1084/jem.20050463
Engelhardt JJ, Boldajipour B, Beemiller P, Pandurangi P, Sorensen C, Werb Z, et al. Marginating dendritic cells of the tumor microenvironment cross-present tumor antigens and stably engage tumor-specific T cells. Cancer Cell. 2012;21:402–17.
pubmed: 22439936
pmcid: 3311997
doi: 10.1016/j.ccr.2012.01.008
Krempski J, Karyampudi L, Behrens MD, Erskine CL, Hartmann L, Dong H, et al. Tumor-infiltrating programmed death receptor-1+ dendritic cells mediate immune suppression in ovarian cancer. J Immunol. 2011;186:6905–13.
pubmed: 21551365
doi: 10.4049/jimmunol.1100274
Freeman GJ, Long AJ, Iwai Y, Bourque K, Chernova T, Nishimura H, et al. Engagement of the PD-1 immunoinhibitory receptor by a novel B7 family member leads to negative regulation of lymphocyte activation. J Exp Med. 2000;192:1027–34.
pubmed: 11015443
pmcid: 2193311
doi: 10.1084/jem.192.7.1027
Greaves P, Gribben JG. The role of B7 family molecules in hematologic malignancy. Blood. 2013;121:734–44.
pubmed: 23223433
pmcid: 3563361
doi: 10.1182/blood-2012-10-385591
Cannons JL, Qi H, Lu KT, Dutta M, Gomez-Rodriguez J, Cheng J, et al. Optimal germinal center responses require a multistage T cell:B cell adhesion process involving integrins, SLAM-associated protein, and CD84. Immunity. 2010;32:253–65.
pubmed: 20153220
pmcid: 2830297
doi: 10.1016/j.immuni.2010.01.010
Kuziel WA, Morgan SJ, Dawson TC, Griffin S, Smithies O, Ley K, et al. Severe reduction in leukocyte adhesion and monocyte extravasation in mice deficient in CC chemokine receptor 2. Proc Natl Acad Sci USA. 1997;94:12053–8.
pubmed: 9342361
doi: 10.1073/pnas.94.22.12053
pmcid: 23699
Brockschnieder D, Pechmann Y, Sonnenberg-Riethmacher E, Riethmacher D. An improved mouse line for Cre-induced cell ablation due to diphtheria toxin A, expressed from the Rosa26 locus. Genesis. 2006;44:322–7.
pubmed: 16791847
doi: 10.1002/dvg.20218
Anders S, Pyl PT, Huber W. HTSeq-a Python framework to work with high-throughput sequencing data. Bioinformatics. 2015;31:166–9.
pubmed: 25260700
doi: 10.1093/bioinformatics/btu638
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.
pubmed: 23104886
Love MI, Huber W, Anders S. Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol. 2014;15:550.
pubmed: 25516281
pmcid: 4302049
doi: 10.1186/s13059-014-0550-8
Varol C, Landsman L, Fogg DK, Greenshtein L, Gildor B, Margalit R, et al. Monocytes give rise to mucosal, but not splenic, conventional dendritic cells. J Exp Med. 2007;204:171–80.
pubmed: 17190836
pmcid: 2118434
doi: 10.1084/jem.20061011