Tumor inherent interferon regulators as biomarkers of long-term chemotherapeutic response in TNBC.
Breast cancer
Prognostic markers
Tumour biomarkers
Journal
NPJ precision oncology
ISSN: 2397-768X
Titre abrégé: NPJ Precis Oncol
Pays: England
ID NLM: 101708166
Informations de publication
Date de publication:
2019
2019
Historique:
received:
07
12
2018
accepted:
09
08
2019
entrez:
5
9
2019
pubmed:
5
9
2019
medline:
5
9
2019
Statut:
epublish
Résumé
Patients diagnosed with triple negative breast cancer (TNBC) have an increased risk of rapid metastasis compared to other subtypes. Predicting long-term survival post-chemotherapy in patients with TNBC is difficult, yet enhanced infiltration of tumor infiltrating lymphocytes (TILs) has been associated with therapeutic response and reduced risk of metastatic relapse. Immune biomarkers that predict the immune state of a tumor and risk of metastatic relapse pre- or mid-neoadjuvant chemotherapy are urgently needed to allow earlier implementation of alternate therapies that may reduce TNBC patient mortality. Utilizing a neoadjuvant chemotherapy trial where TNBC patients had sequential biopsies taken, we demonstrate that measurement of T-cell subsets and effector function, specifically CD45RO expression, throughout chemotherapy predicts risk of metastatic relapse. Furthermore, we identified the tumor inherent interferon regulatory factor IRF9 as a marker of active intratumoral type I and II interferon (IFN) signaling and reduced risk of distant relapse. Functional implications of tumor intrinsic IFN signaling were demonstrated using an immunocompetent mouse model of TNBC, where enhanced type I IFN signaling increased anti-tumor immunity and metastasis-free survival post-chemotherapy. Using two independent adjuvant cohorts we were able to validate loss of IRF9 as a poor prognostic biomarker pre-chemotherapy. Thus, IRF9 expression may offer early insight into TNBC patient prognosis and tumor heat, allowing for identification of patients that are unlikely to respond to chemotherapy alone and could benefit from further immune-based therapeutic intervention.
Identifiants
pubmed: 31482136
doi: 10.1038/s41698-019-0093-2
pii: 93
pmc: PMC6715634
doi:
Types de publication
Journal Article
Langues
eng
Pagination
21Déclaration de conflit d'intérêts
Competing interestS.O.T. has received honoraria for serving on advisory boards for AstraZeneca, BMS, and Merck. B.S.P. receives collaborative funding for another project from AstraZeneca/MedImmune. B.S.P. is sole inventor on patent application PCT/AU2016/050392 that covers the method of diagnosis of breast cancer (IRF9). Remaining authors declare no competing interests.
Références
Ann Oncol. 2012 May;23(5):1301-1306
pubmed: 21917737
Nat Rev Cancer. 2016 Mar;16(3):131-44
pubmed: 26911188
Genome Biol. 2010;11(3):R25
pubmed: 20196867
Cytokine. 2019 Jun;118:42-47
pubmed: 29681426
J Clin Oncol. 2011 May 20;29(15):1949-55
pubmed: 21483002
Cell Rep. 2016 Apr 5;15(1):171-180
pubmed: 27052162
Adv Radiat Oncol. 2017 Feb 07;2(2):105-109
pubmed: 28740920
Sci Transl Med. 2013 Aug 28;5(200):200ra116
pubmed: 23986400
Nat Rev Clin Oncol. 2011 Mar;8(3):151-60
pubmed: 21364688
Nucleic Acids Res. 2012 Sep 1;40(17):e133
pubmed: 22638577
Nucleic Acids Res. 2015 Sep 3;43(15):e97
pubmed: 25925576
Cancer Cell. 2017 Feb 13;31(2):194-207
pubmed: 28196594
Ann Oncol. 2015 Feb;26(2):259-71
pubmed: 25214542
Bioinformatics. 2010 Sep 1;26(17):2176-82
pubmed: 20610611
Mol Cancer Res. 2005 Jan;3(1):1-13
pubmed: 15671244
Cancer Discov. 2016 Dec;6(12):1382-1399
pubmed: 27663893
Nat Med. 2014 Nov;20(11):1301-9
pubmed: 25344738
Cancer Res. 2011 Jun 1;71(11):4002-14
pubmed: 21632555
Cancer Immunol Res. 2017 Oct;5(10):871-884
pubmed: 28848054
Nat Med. 2012 Aug;18(8):1224-31
pubmed: 22820642
Nat Med. 2018 Jul;24(7):986-993
pubmed: 29942092
Science. 2006 Sep 29;313(5795):1960-4
pubmed: 17008531
Proc Natl Acad Sci U S A. 2016 Nov 29;113(48):E7759-E7768
pubmed: 27837020
Nat Immunol. 2005 Jul;6(7):722-9
pubmed: 15951814
Bioinformatics. 2005 May 1;21(9):2067-75
pubmed: 15657102
J Clin Oncol. 2010 Jan 1;28(1):105-13
pubmed: 19917869
Br J Cancer. 2016 Jan 19;114(2):177-87
pubmed: 26695443
J Clin Oncol. 2013 Mar 1;31(7):860-7
pubmed: 23341518
Front Oncol. 2017 Aug 03;7:156
pubmed: 28824872
J Clin Oncol. 2012 May 20;30(15):1796-804
pubmed: 22508812
Cancer Discov. 2014 Jun;4(6):674-87
pubmed: 24589924
Nat Rev Cancer. 2017 May;17(5):286-301
pubmed: 28338065
Clin Exp Metastasis. 1999 Mar;17(2):163-70
pubmed: 10411109
PLoS One. 2013 Nov 14;8(11):e80063
pubmed: 24244610
Br J Cancer. 2002 Apr 8;86(7):1041-6
pubmed: 11953845
Cancer J. 2010 Jul-Aug;16(4):399-403
pubmed: 20693853
Nat Rev Immunol. 2006 Nov;6(11):836-48
pubmed: 17063185
Ann Oncol. 2014 Aug;25(8):1536-43
pubmed: 24915873
J Exp Med. 2011 Sep 26;208(10):2005-16
pubmed: 21930765
Nature. 2000 Aug 17;406(6797):747-52
pubmed: 10963602
Nucleic Acids Res. 2015 Apr 20;43(7):e47
pubmed: 25605792
Annu Rev Immunol. 2013;31:51-72
pubmed: 23157435
Ann Appl Stat. 2016 Jun;10(2):946-963
pubmed: 28367255
Cancer Immunol Res. 2015 Nov;3(11):1207-17
pubmed: 26198985
Cancer Res. 1986 Aug;46(8 Suppl):4244s-4248s
pubmed: 3524805
Oncoimmunology. 2015 Sep 2;5(3):e1088631
pubmed: 27141345
Clin Cancer Res. 2007 Aug 1;13(15 Pt 1):4429-34
pubmed: 17671126
J Thorac Oncol. 2016 Jun;11(6):789-800
pubmed: 26845192
Cancer Immunol Res. 2015 Apr;3(4):326-32
pubmed: 25527356
Cancer Res. 2011 Apr 1;71(7):2488-96
pubmed: 21300764
Cell Syst. 2015 Dec 23;1(6):417-425
pubmed: 26771021
BMC Bioinformatics. 2011 Aug 04;12:323
pubmed: 21816040
Proc Natl Acad Sci U S A. 2005 Oct 25;102(43):15545-50
pubmed: 16199517
N Engl J Med. 2005 Dec 22;353(25):2654-66
pubmed: 16371631
Eur J Pharmacol. 2013 Oct 5;717(1-3):58-66
pubmed: 23545358
Histopathology. 2016 Jul;69(1):25-34
pubmed: 26588661
Bioinformatics. 2013 Jan 1;29(1):15-21
pubmed: 23104886
Nat Rev Cancer. 2012 Mar 15;12(4):298-306
pubmed: 22419253
J Clin Pathol. 2006 Jul;59(7):729-35
pubmed: 16556664
J Clin Oncol. 2008 Mar 10;26(8):1275-81
pubmed: 18250347