Digital Pathology Analysis Quantifies Spatial Heterogeneity of CD3, CD4, CD8, CD20, and FoxP3 Immune Markers in Triple-Negative Breast Cancer.
QuPath
breast cancer
digital pathology
image informatics
immuno-architecture
spatial patterns
tumor heterogeneity
Journal
Frontiers in physiology
ISSN: 1664-042X
Titre abrégé: Front Physiol
Pays: Switzerland
ID NLM: 101549006
Informations de publication
Date de publication:
2020
2020
Historique:
received:
14
07
2020
accepted:
24
09
2020
entrez:
16
11
2020
pubmed:
17
11
2020
medline:
17
11
2020
Statut:
epublish
Résumé
Overwhelming evidence has shown the significant role of the tumor microenvironment (TME) in governing the triple-negative breast cancer (TNBC) progression. Digital pathology can provide key information about the spatial heterogeneity within the TME using image analysis and spatial statistics. These analyses have been applied to CD8+ T cells, but quantitative analyses of other important markers and their correlations are limited. In this study, a digital pathology computational workflow is formulated for characterizing the spatial distributions of five immune markers (CD3, CD4, CD8, CD20, and FoxP3) and then the functionality is tested on whole slide images from patients with TNBC. The workflow is initiated by digital image processing to extract and colocalize immune marker-labeled cells and then convert this information to point patterns. Afterward invasive front (IF), central tumor (CT), and normal tissue (N) are characterized. For each region, we examine the intra-tumoral heterogeneity. The workflow is then repeated for all specimens to capture inter-tumoral heterogeneity. In this study, both intra- and inter-tumoral heterogeneities are observed for all five markers across all specimens. Among all regions, IF tends to have higher densities of immune cells and overall larger variations in spatial model fitting parameters and higher density in cell clusters and hotspots compared to CT and N. Results suggest a distinct role of IF in the tumor immuno-architecture. Though the sample size is limited in the study, the computational workflow could be readily reproduced and scaled due to its automatic nature. Importantly, the value of the workflow also lies in its potential to be linked to treatment outcomes and identification of predictive biomarkers for responders/non-responders, and its application to parameterization and validation of computational immuno-oncology models.
Identifiants
pubmed: 33192595
doi: 10.3389/fphys.2020.583333
pmc: PMC7604437
doi:
Types de publication
Journal Article
Langues
eng
Pagination
583333Subventions
Organisme : NCI NIH HHS
ID : R01 CA138264
Pays : United States
Organisme : NCI NIH HHS
ID : U01 CA212007
Pays : United States
Informations de copyright
Copyright © 2020 Mi, Gong, Sulam, Fertig, Szalay, Jaffee, Stearns, Emens, Cimino-Mathews and Popel.
Références
Cancer Biol Ther. 2018 Apr 3;19(4):296-305
pubmed: 29313457
AAPS J. 2019 Jun 3;21(4):72
pubmed: 31161268
Histopathology. 2012 Jul;61(1):1-9
pubmed: 21477260
BMC Syst Biol. 2017 Jul 11;11(1):68
pubmed: 28693495
Cancer Res. 2011 Sep 1;71(17):5670-7
pubmed: 21846824
Processes (Basel). 2019 Jan;7(1):
pubmed: 30701168
Sci Transl Med. 2019 May 29;11(494):
pubmed: 31142678
Cancer Immunol Immunother. 2006 Apr;55(4):451-8
pubmed: 16034562
J Clin Oncol. 2016 Mar 10;34(8):871-8
pubmed: 26811525
Cell Rep. 2020 Jan 14;30(2):481-496.e6
pubmed: 31940491
Front Oncol. 2019 Jan 07;8:649
pubmed: 30666298
Proc Natl Acad Sci U S A. 2019 Aug 6;116(32):16046-16055
pubmed: 31341086
CPT Pharmacometrics Syst Pharmacol. 2020 Jul 2;:
pubmed: 32618119
NPJ Breast Cancer. 2018 Dec 10;4:40
pubmed: 30564631
Cancer. 2008 Sep 15;113(6):1387-95
pubmed: 18671239
Sci Rep. 2019 Aug 2;9(1):11286
pubmed: 31375756
Breast Cancer Res. 2016 Jul 29;18(1):78
pubmed: 27473061
Nat Protoc. 2019 Oct;14(10):2900-2930
pubmed: 31534232
Cancer Inform. 2018 Jun 28;17:1176935118782880
pubmed: 30013304
Cancer Res. 2017 Nov 15;77(22):6442-6452
pubmed: 28923860
J R Soc Interface. 2017 Sep;14(134):
pubmed: 28931635
AAPS J. 2019 Jun 24;21(5):79
pubmed: 31236847
J Clin Oncol. 2006 Dec 1;24(34):5373-80
pubmed: 17135638
Trends Cell Biol. 2015 Apr;25(4):198-213
pubmed: 25540894
AAPS J. 2020 Jun 12;22(4):85
pubmed: 32533270
PLoS Comput Biol. 2019 Sep 10;15(9):e1007344
pubmed: 31504033
Proc Natl Acad Sci U S A. 2019 Feb 26;116(9):3678-3687
pubmed: 30733298
Prog Neurobiol. 1991;37(5):433-74
pubmed: 1754688
Biometrics. 2007 Mar;63(1):252-8
pubmed: 17447951
Methods Enzymol. 2009;467:79-109
pubmed: 19897090
Sci Rep. 2019 Jun 25;9(1):9211
pubmed: 31239476
Adv Anat Pathol. 2017 Nov;24(6):311-335
pubmed: 28777143
Lancet Oncol. 2020 Jan;21(1):44-59
pubmed: 31786121
Front Bioeng Biotechnol. 2020 Feb 25;8:141
pubmed: 32158754
EBioMedicine. 2018 Jan;27:317-328
pubmed: 29292031
AAPS J. 2017 Jul;19(4):1002-1016
pubmed: 28540623
Biometrika. 1949 Jun;36(Pt. 1-2):18-25
pubmed: 18146215
Nat Methods. 2020 Mar;17(3):261-272
pubmed: 32015543
Clin Cancer Res. 2014 Dec 1;20(23):5995-6005
pubmed: 25255793
Sci Rep. 2017 Dec 4;7(1):16878
pubmed: 29203879
R Soc Open Sci. 2019 May 22;6(5):190366
pubmed: 31218069
Nat Commun. 2017 Sep 4;8(1):420
pubmed: 28871082
Bull Math Biol. 2018 May;80(5):1134-1171
pubmed: 29568983
Histopathology. 2020 Jul;77(1):79-91
pubmed: 32281132
Sci Transl Med. 2019 Jun 5;11(495):
pubmed: 31167928
Cytometry B Clin Cytom. 2010 Mar;78(2):105-14
pubmed: 19834968
Front Oncol. 2018 Dec 18;8:627
pubmed: 30619761
Cell. 2018 Jun 14;173(7):1755-1769.e22
pubmed: 29754820
Lancet Oncol. 2018 Jan;19(1):40-50
pubmed: 29233559
Sci Rep. 2019 Mar 27;9(1):5276
pubmed: 30918274
Biom J. 2008 Feb;50(1):43-57
pubmed: 17640081
Hum Pathol. 2016 Jan;47(1):52-63
pubmed: 26527522
J Clin Pathol. 1981 Oct;34(10):1083-90
pubmed: 6975780
Lab Invest. 2018 Jan;98(1):15-26
pubmed: 29251737
N Engl J Med. 2019 Mar 21;380(12):1103-1115
pubmed: 30779531
J Biomed Opt. 2009 Nov-Dec;14(6):064036
pubmed: 20059274
Nat Commun. 2019 Nov 29;10(1):5440
pubmed: 31784511
Cancer Res. 2019 May 1;79(9):2435-2444
pubmed: 30894376
Br J Cancer. 2020 Feb;122(4):539-544
pubmed: 31806878
Mol Biol Cell. 2016 Nov 7;27(22):3627-3636
pubmed: 27582387
J Theor Biol. 2018 Sep 7;452:56-68
pubmed: 29750999
J Cell Biol. 1966 Jul;30(1):23-38
pubmed: 5338131
Oncologist. 2020 Jan;25(1):64-77
pubmed: 31138727
Cold Spring Harb Perspect Med. 2016 Aug 01;6(8):
pubmed: 27481837
Sci Transl Med. 2011 Nov 9;3(108):108ra113
pubmed: 22072638
J Clin Oncol. 2009 Dec 10;27(35):5944-51
pubmed: 19858404
Prog Biophys Mol Biol. 2018 Nov;139:15-22
pubmed: 29902482
Cancer Immunol Immunother. 2010 May;59(5):653-61
pubmed: 19908042
Theor Biol Med Model. 2013 Jun 21;10:41
pubmed: 23800293
PLoS Comput Biol. 2015 Apr 23;11(4):e1004181
pubmed: 25905470
Cancer Res. 2011 Sep 1;71(17):5601-5
pubmed: 21846822
Adv Radiat Oncol. 2018 Sep 07;4(1):177-185
pubmed: 30706026
Pigment Cell Melanoma Res. 2015 Sep;28(5):490-500
pubmed: 25818762
Clin Cancer Res. 2019 Apr 15;25(8):2442-2449
pubmed: 30617133
Biophys J. 2007 Jun 15;92(12):4196-208
pubmed: 17384077
Nat Methods. 2012 Jun 28;9(7):690-6
pubmed: 22743774
Lab Invest. 2019 Jan;99(1):107-117
pubmed: 30181553