Immune profiles in acute myeloid leukemia bone marrow associate with patient age, T-cell receptor clonality, and survival.
Journal
Blood advances
ISSN: 2473-9537
Titre abrégé: Blood Adv
Pays: United States
ID NLM: 101698425
Informations de publication
Date de publication:
28 01 2020
28 01 2020
Historique:
received:
02
08
2019
accepted:
31
10
2019
entrez:
23
1
2020
pubmed:
23
1
2020
medline:
15
4
2021
Statut:
ppublish
Résumé
The immunologic microenvironment in various solid tumors is aberrant and correlates with clinical survival. Here, we present a comprehensive analysis of the immune environment of acute myeloid leukemia (AML) bone marrow (BM) at diagnosis. We compared the immunologic landscape of formalin-fixed paraffin-embedded BM trephine samples from AML (n = 69), chronic myeloid leukemia (CML; n = 56), and B-cell acute lymphoblastic leukemia (B-ALL) patients (n = 52) at diagnosis to controls (n = 12) with 30 immunophenotype markers using multiplex immunohistochemistry and computerized image analysis. We identified distinct immunologic profiles specific for leukemia subtypes and controls enabling accurate classification of AML (area under the curve [AUC] = 1.0), CML (AUC = 0.99), B-ALL (AUC = 0.96), and control subjects (AUC = 1.0). Interestingly, 2 major immunologic AML clusters differing in age, T-cell receptor clonality, and survival were discovered. A low proportion of regulatory T cells and pSTAT1+cMAF- monocytes were identified as novel biomarkers of superior event-free survival in intensively treated AML patients. Moreover, we demonstrated that AML BM and peripheral blood samples are dissimilar in terms of immune cell phenotypes. To conclude, our study shows that the immunologic landscape considerably varies by leukemia subtype suggesting disease-specific immunoregulation. Furthermore, the association of the AML immune microenvironment with clinical parameters suggests a rationale for including immunologic parameters to improve disease classification or even patient risk stratification.
Identifiants
pubmed: 31968078
pii: S2473-9529(20)31658-X
doi: 10.1182/bloodadvances.2019000792
pmc: PMC6988390
doi:
Substances chimiques
Receptors, Antigen, T-Cell
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
274-286Informations de copyright
© 2020 by The American Society of Hematology.
Références
Nat Rev Immunol. 2008 Jan;8(1):59-73
pubmed: 18097448
Immunol Rev. 2006 Oct;213:131-45
pubmed: 16972901
J Hematol Oncol. 2015 Jul 30;8:93
pubmed: 26219463
Cell. 2011 Mar 4;144(5):646-74
pubmed: 21376230
N Engl J Med. 2014 Oct 16;371(16):1507-17
pubmed: 25317870
Nat Rev Immunol. 2012 Mar 22;12(4):269-81
pubmed: 22437939
Cancer. 2019 May 1;125(9):1470-1481
pubmed: 30500073
Leukemia. 2018 Jul;32(7):1643-1656
pubmed: 29925907
Haematologica. 2016 Oct;101(10):1216-1227
pubmed: 27390361
Leukemia. 2016 Aug;30(8):1638-47
pubmed: 27133824
N Engl J Med. 2018 Feb 1;378(5):449-459
pubmed: 29385376
Blood. 2009 Oct 29;114(18):3909-16
pubmed: 19710498
Lancet Oncol. 2017 Jan;18(1):132-142
pubmed: 27864015
N Engl J Med. 2017 Mar 2;376(9):836-847
pubmed: 28249141
J Clin Invest. 1998 Feb 15;101(4):746-54
pubmed: 9466968
J Immunol. 2001 Nov 15;167(10):6021-30
pubmed: 11698483
N Engl J Med. 2015 Jan 22;372(4):320-30
pubmed: 25399552
J Transl Med. 2012 Oct 03;10:205
pubmed: 23034130
Clin Cancer Res. 2009 May 15;15(10):3325-32
pubmed: 19417016
Semin Immunol. 2007 Oct;19(5):331-40
pubmed: 18024073
Nat Rev Immunol. 2004 Feb;4(2):123-32
pubmed: 15040585
N Engl J Med. 2012 Mar 22;366(12):1079-89
pubmed: 22417203
Sci Rep. 2017 Nov 14;7(1):15580
pubmed: 29138507
Leukemia. 2014 Jun;28(6):1280-8
pubmed: 24270737
Blood. 1991 Apr 1;77(7):1429-35
pubmed: 2009367
Nat Rev Immunol. 2008 Jul;8(7):512-22
pubmed: 18469829
Cancer Discov. 2019 Mar;9(3):370-383
pubmed: 30409776
Curr Hematol Malig Rep. 2015 Jun;10(2):96-103
pubmed: 25921386
Sci Rep. 2017 Jan 13;7:40707
pubmed: 28084439
N Engl J Med. 2016 Jun 9;374(23):2209-2221
pubmed: 27276561
Proc Natl Acad Sci U S A. 2012 Dec 26;109(52):21432-7
pubmed: 23236163
Sci Rep. 2015 Dec 17;5:18411
pubmed: 26674118
Leukemia. 2019 Jul;33(7):1570-1582
pubmed: 30635636
Leukemia. 2017 May;31(5):1108-1116
pubmed: 27890936
Leukemia. 2001 Jan;15(1):128-33
pubmed: 11243380
J Immunol. 2015 Sep 15;195(6):2580-90
pubmed: 26246143
J Clin Invest. 2010 Apr;120(4):1111-24
pubmed: 20234093
Nat Rev Cancer. 2012 Mar 15;12(4):298-306
pubmed: 22419253
J Immunol. 2008 Mar 15;180(6):3739-45
pubmed: 18322179
Science. 2015 Apr 3;348(6230):74-80
pubmed: 25838376
IEEE Trans Image Process. 1996;5(8):1266-71
pubmed: 18285214
Blood. 2017 Jan 26;129(4):424-447
pubmed: 27895058
Nat Methods. 2017 Aug 31;14(9):849-863
pubmed: 28858338
Immunity. 2013 Jul 25;39(1):1-10
pubmed: 23890059
Nat Commun. 2016 Jul 06;7:12150
pubmed: 27381735
Nat Rev Cancer. 2012 Mar 22;12(4):252-64
pubmed: 22437870
Anal Quant Cytol Histol. 2001 Aug;23(4):291-9
pubmed: 11531144
J Clin Invest. 2009 Oct;119(10):3070-8
pubmed: 19770514
Blood. 2003 Apr 1;101(7):2711-20
pubmed: 12433688
Nat Rev Clin Oncol. 2011 Mar;8(3):151-60
pubmed: 21364688
Nat Immunol. 2013 Oct;14(10):1014-22
pubmed: 24048123
IEEE Rev Biomed Eng. 2016;9:234-63
pubmed: 26742143
Lancet Oncol. 2018 Jun;19(6):747-757
pubmed: 29735299
Blood. 2017 Feb 16;129(7):811-822
pubmed: 28064238
Genome Biol. 2006;7(10):R100
pubmed: 17076895
Nat Rev Immunol. 2012 Mar 22;12(4):253-68
pubmed: 22437938
Nat Med. 2013 Nov;19(11):1513-7
pubmed: 24162813
Front Immunol. 2017 Apr 24;8:469
pubmed: 28484463