An immunological signature to predict outcome in patients with triple-negative breast cancer with residual disease after neoadjuvant chemotherapy.
residual disease
transcriptomic signature
triple-negative breast cancer
tumor immune microenvironment
Journal
ESMO open
ISSN: 2059-7029
Titre abrégé: ESMO Open
Pays: England
ID NLM: 101690685
Informations de publication
Date de publication:
08 2022
08 2022
Historique:
received:
06
04
2022
accepted:
22
04
2022
pubmed:
28
6
2022
medline:
31
8
2022
entrez:
27
6
2022
Statut:
ppublish
Résumé
When triple-negative breast cancer (TNBC) patients have residual disease after neoadjuvant chemotherapy (NACT), they have a high risk of metastatic relapse. With immune infiltrate in TNBC being prognostic and predictive of response to treatment, our aim was to develop an immunologic transcriptomic signature using post-NACT samples to predict relapse. We identified 115 samples of residual tumors from post-NACT TNBC patients. We profiled the expression of 770 genes related to cancer microenvironment using the NanoString PanCancer IO360 panel to develop a prognostic transcriptomic signature, and we describe the immune microenvironments of the residual tumors. Thirty-eight (33%) patients experienced metastatic relapse. Hierarchical clustering separated patients into five clusters with distinct prognosis based on pathways linked to immune activation, epithelial-to-mesenchymal transition and cell cycle. The immune microenvironment of the residual disease was significantly different between patients who experienced relapse compared to those who did not, the latter having significantly more effector antitumoral immune cells, with significant differences in lymphoid subpopulations. We selected eight genes linked to immunity (BLK, GZMM, CXCR6, LILRA1, SPIB, CCL4, CXCR4, SLAMF7) to develop a transcriptomic signature which could predict relapse in our cohort. This signature was validated in two external cohorts (KMplot and METABRIC). Lack of immune activation after NACT is associated with a high risk of distant relapse. We propose a prognostic signature based on immune infiltrate that could lead to targeted therapeutic strategies to improve patient prognosis.
Sections du résumé
BACKGROUND
When triple-negative breast cancer (TNBC) patients have residual disease after neoadjuvant chemotherapy (NACT), they have a high risk of metastatic relapse. With immune infiltrate in TNBC being prognostic and predictive of response to treatment, our aim was to develop an immunologic transcriptomic signature using post-NACT samples to predict relapse.
MATERIALS AND METHODS
We identified 115 samples of residual tumors from post-NACT TNBC patients. We profiled the expression of 770 genes related to cancer microenvironment using the NanoString PanCancer IO360 panel to develop a prognostic transcriptomic signature, and we describe the immune microenvironments of the residual tumors.
RESULTS
Thirty-eight (33%) patients experienced metastatic relapse. Hierarchical clustering separated patients into five clusters with distinct prognosis based on pathways linked to immune activation, epithelial-to-mesenchymal transition and cell cycle. The immune microenvironment of the residual disease was significantly different between patients who experienced relapse compared to those who did not, the latter having significantly more effector antitumoral immune cells, with significant differences in lymphoid subpopulations. We selected eight genes linked to immunity (BLK, GZMM, CXCR6, LILRA1, SPIB, CCL4, CXCR4, SLAMF7) to develop a transcriptomic signature which could predict relapse in our cohort. This signature was validated in two external cohorts (KMplot and METABRIC).
CONCLUSIONS
Lack of immune activation after NACT is associated with a high risk of distant relapse. We propose a prognostic signature based on immune infiltrate that could lead to targeted therapeutic strategies to improve patient prognosis.
Identifiants
pubmed: 35759853
pii: S2059-7029(22)00122-3
doi: 10.1016/j.esmoop.2022.100502
pmc: PMC9434232
pii:
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
100502Informations de copyright
Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.
Déclaration de conflit d'intérêts
Disclosure The authors have declared no conflicts of interest.
Références
Ann Oncol. 2014 Jun;25(6):1128-36
pubmed: 24618153
J Clin Oncol. 2014 Sep 20;32(27):2959-66
pubmed: 25071121
Lancet. 2020 Dec 5;396(10265):1817-1828
pubmed: 33278935
Semin Cancer Biol. 2018 Oct;52(Pt 2):16-25
pubmed: 29024776
Bioinformatics. 2012 Jun 1;28(11):1546-8
pubmed: 22513995
Arch Pathol Lab Med. 2010 Jul;134(7):e48-72
pubmed: 20586616
Breast Cancer Res Treat. 2020 Jan;179(1):11-23
pubmed: 31529299
Proc Natl Acad Sci U S A. 2005 Oct 25;102(43):15545-50
pubmed: 16199517
Ann Oncol. 2019 Aug 1;30(8):1279-1288
pubmed: 31095287
J Clin Oncol. 2015 Mar 20;33(9):983-91
pubmed: 25534375
N Engl J Med. 2017 Jun 1;376(22):2147-2159
pubmed: 28564564
Ann Oncol. 2019 Feb 1;30(2):236-242
pubmed: 30590484
Nature. 2012 Apr 18;486(7403):346-52
pubmed: 22522925
N Engl J Med. 2018 Nov 29;379(22):2108-2121
pubmed: 30345906
J Clin Invest. 2017 Aug 1;127(8):2930-2940
pubmed: 28650338
Oncoimmunology. 2017 Feb 6;6(2):e1253654
pubmed: 28344865
Mod Pathol. 2015 Sep;28(9):1185-201
pubmed: 26205180
Ann Oncol. 2014 Mar;25(3):611-618
pubmed: 24401929
Nat Med. 2019 Jun;25(6):920-928
pubmed: 31086347
OMICS. 2012 May;16(5):284-7
pubmed: 22455463
J Clin Oncol. 2013 Mar 1;31(7):860-7
pubmed: 23341518
J Clin Oncol. 2012 May 20;30(15):1796-804
pubmed: 22508812
Lancet. 2020 Oct 10;396(10257):1090-1100
pubmed: 32966830
Nat Biotechnol. 2020 Jun;38(6):675-678
pubmed: 32444850
Clin Cancer Res. 2007 Aug 1;13(15 Pt 1):4429-34
pubmed: 17671126
J Clin Oncol. 2019 Mar 1;37(7):559-569
pubmed: 30650045
Genome Biol. 2016 Oct 20;17(1):218
pubmed: 27765066
Nat Commun. 2020 Dec 11;11(1):6357
pubmed: 33311473
J Clin Oncol. 2007 Oct 1;25(28):4414-22
pubmed: 17785706
Ann Pathol. 2014 Oct;34(5):352-65
pubmed: 25439988
BMC Bioinformatics. 2013 Jan 16;14:7
pubmed: 23323831
J Exp Med. 2005 Dec 19;202(12):1691-701
pubmed: 16365148
Lancet. 2014 Jul 12;384(9938):164-72
pubmed: 24529560
Cancer Cell. 2006 Dec;10(6):529-41
pubmed: 17157792
Clin Cancer Res. 2016 Mar 15;22(6):1499-509
pubmed: 26515496
Comput Struct Biotechnol J. 2021 Jul 18;19:4101-4109
pubmed: 34527184
Am J Pathol. 2011 Jul;179(1):37-45
pubmed: 21703392
J Clin Oncol. 2006 Sep 10;24(26):4236-44
pubmed: 16896004
N Engl J Med. 2020 Feb 27;382(9):810-821
pubmed: 32101663
JAMA. 2021 Jan 5;325(1):50-58
pubmed: 33300950
N Engl J Med. 2021 Jun 24;384(25):2394-2405
pubmed: 34081848
J Clin Oncol. 2008 Mar 10;26(8):1275-81
pubmed: 18250347