Intratumoral, rather than stromal, CD8+ T cells could be a potential negative prognostic marker in invasive breast cancer patients.
Journal
Translational oncology
ISSN: 1936-5233
Titre abrégé: Transl Oncol
Pays: United States
ID NLM: 101472619
Informations de publication
Date de publication:
Mar 2019
Mar 2019
Historique:
received:
26
10
2018
revised:
07
12
2018
accepted:
10
12
2018
pubmed:
27
1
2019
medline:
27
1
2019
entrez:
26
1
2019
Statut:
ppublish
Résumé
Tumor infiltrating lymphocytes (TILs) are widely considered a key sign of the immune interaction between host and tumor, and potentially prognostic biomarkers of good or bad outcome in many cancers, included invasive breast cancer (BC). However, results about the association between TIL typology, location and BC prognosis, are controversial. The aim of the study was to evaluated the prognostic significance of TIL subtypes (CD4+, CD8+, FOXP3+ T cells) and their location (stromal "s" and intratumoral "i" CD4+ and CD8+) in BC patients, focusing on the association between these markers and immunocheckpoint molecules such as cytotoxic T lymphocyte antigen 4 (CTLA-4), programmed cell death ligand 1 (PD-L1) and its receptor (PD-1). CD4+, CD8+, FOXP3+, CTLA4+, PD-L1+ and PD-1+ expression was examined by immunohistochemistry on tissue microarrays (TMAs) from 180 BC patients. Univariate and Kaplan-Meier analyses of disease free survival (DFS) were performed to evaluate the prognostic significance of marker expression. Total CD8+ T cells were not significantly associated with DFS. Differently, patients with iCD8+ and sCD8+ overexpression showed a trend toward respectively a worse (P = .050) and a better 5-years DFS (P = .064). Interestingly, TIL expression of both PD-1+ and PD-L1+, was significantly associated with iCD8+ (P = .0004; P < .0001 respectively), while only TIL expression of PD-1 was associated with sCD8+ (P = .001). Our data show that iCD8+ T cells, but no sCD8+ T cells identify a subgroup of patients with poor DFS and this could be due to the overexpression of PD-L1/PD-1 pathway.
Sections du résumé
BACKGROUND
BACKGROUND
Tumor infiltrating lymphocytes (TILs) are widely considered a key sign of the immune interaction between host and tumor, and potentially prognostic biomarkers of good or bad outcome in many cancers, included invasive breast cancer (BC). However, results about the association between TIL typology, location and BC prognosis, are controversial. The aim of the study was to evaluated the prognostic significance of TIL subtypes (CD4+, CD8+, FOXP3+ T cells) and their location (stromal "s" and intratumoral "i" CD4+ and CD8+) in BC patients, focusing on the association between these markers and immunocheckpoint molecules such as cytotoxic T lymphocyte antigen 4 (CTLA-4), programmed cell death ligand 1 (PD-L1) and its receptor (PD-1).
METHODS
METHODS
CD4+, CD8+, FOXP3+, CTLA4+, PD-L1+ and PD-1+ expression was examined by immunohistochemistry on tissue microarrays (TMAs) from 180 BC patients. Univariate and Kaplan-Meier analyses of disease free survival (DFS) were performed to evaluate the prognostic significance of marker expression.
RESULTS
RESULTS
Total CD8+ T cells were not significantly associated with DFS. Differently, patients with iCD8+ and sCD8+ overexpression showed a trend toward respectively a worse (P = .050) and a better 5-years DFS (P = .064). Interestingly, TIL expression of both PD-1+ and PD-L1+, was significantly associated with iCD8+ (P = .0004; P < .0001 respectively), while only TIL expression of PD-1 was associated with sCD8+ (P = .001).
CONCLUSION
CONCLUSIONS
Our data show that iCD8+ T cells, but no sCD8+ T cells identify a subgroup of patients with poor DFS and this could be due to the overexpression of PD-L1/PD-1 pathway.
Identifiants
pubmed: 30682679
pii: S1936-5233(18)30546-1
doi: 10.1016/j.tranon.2018.12.005
pmc: PMC6350084
pii:
doi:
Types de publication
Journal Article
Langues
eng
Pagination
585-595Informations de copyright
Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.
Références
Cancer Res. 2001 Jul 1;61(13):5132-6
pubmed: 11431351
Nat Immunol. 2002 Nov;3(11):991-8
pubmed: 12407406
Cancer Res. 2003 Apr 1;63(7):1555-9
pubmed: 12670904
Pancreas. 2004 Jan;28(1):e26-31
pubmed: 14707745
J Clin Oncol. 2007 Jan 1;25(1):118-45
pubmed: 17159189
Cancer. 2008 Sep 15;113(6):1387-95
pubmed: 18671239
J Clin Oncol. 2009 Dec 10;27(35):5944-51
pubmed: 19858404
J Exp Clin Cancer Res. 2010 May 13;29:48
pubmed: 20465843
Breast Cancer Res Treat. 2011 May;127(1):99-108
pubmed: 20556505
Breast Cancer Res Treat. 2011 Nov;130(2):645-55
pubmed: 21717105
Clin Immunol. 2011 Dec;141(3):338-47
pubmed: 21955569
Genes Dev. 2011 Dec 15;25(24):2559-72
pubmed: 22190457
Breast Cancer Res. 2012 Mar 15;14(2):R48
pubmed: 22420471
Breast Cancer Res Treat. 2012 Nov;136(1):107-16
pubmed: 22986814
Br J Cancer. 2013 Jan 15;108(1):155-62
pubmed: 23169287
Breast Cancer Res Treat. 2013 Jun;139(3):667-76
pubmed: 23756627
PLoS One. 2014 Apr 17;9(4):e95475
pubmed: 24743335
Breast Cancer Res Treat. 2014 Jul;146(1):15-24
pubmed: 24842267
Ann Oncol. 2014 Aug;25(8):1536-43
pubmed: 24915873
Ann Oncol. 2015 Feb;26(2):259-71
pubmed: 25214542
Cancer Epidemiol Biomarkers Prev. 2014 Dec;23(12):2965-70
pubmed: 25392179
Cancer Immunol Immunother. 2015 Jul;64(7):853-60
pubmed: 25893809
Breast Cancer Res. 2015 Sep 04;17:124
pubmed: 26341640
Hum Pathol. 2016 Jan;47(1):78-84
pubmed: 26541326
J Exp Clin Cancer Res. 2015 Nov 18;34:141
pubmed: 26581194
PLoS One. 2016 Apr 13;11(4):e0152500
pubmed: 27073890
Breast Cancer. 2017 Jan;24(1):3-15
pubmed: 27138387
Asian Pac J Cancer Prev. 2016;17(S3):43-6
pubmed: 27165206
Am J Clin Pathol. 2016 Oct;146(4):496-502
pubmed: 27686176
Int J Cancer. 2017 Mar 15;140(6):1384-1395
pubmed: 27925176
J Clin Pathol. 2017 Oct;70(10):860-867
pubmed: 28373294
Oncotarget. 2017 May 16;8(20):33159-33171
pubmed: 28388539
Oncotarget. 2017 May 9;8(19):31347-31354
pubmed: 28430626
ESMO Open. 2017 May 2;2(2):e000150
pubmed: 28761741
Oncotarget. 2017 May 30;8(31):51641-51651
pubmed: 28881675
Hum Pathol. 2017 Nov;69:110-117
pubmed: 28993275
Oncotarget. 2017 Jul 22;8(39):65730-65742
pubmed: 29029467
Oncotarget. 2017 Aug 12;8(48):83986-83994
pubmed: 29137398
Cell Immunol. 2018 Jan 30;:null
pubmed: 29395859
J Exp Clin Cancer Res. 2018 May 2;37(1):96
pubmed: 29716631