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Unmasking the immune microecology of ductal carcinoma in situ with deep learning

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Narayanan, Priya Lakshami, Raza, Shan-e-Ahmed, Hall, Allison H., Marks, Jeffrey R. , King, Lorraine , West, Robert B. , Hernandez, Lucia , Guppy, Naomi , Dowsett, Mitch , Gusterson, Barry , Maley, Carlo , Hwang, E. Shelley and Yuan, Yinyin (2021) Unmasking the immune microecology of ductal carcinoma in situ with deep learning. npj Breast Cancer , 7 . 19. doi:10.1038/s41523-020-00205-5

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Official URL: https://doi.org/10.1038/s41523-020-00205-5

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Abstract

Despite increasing evidence supporting the clinical relevance of tumour infiltrating lymphocytes (TILs) in invasive breast cancer, TIL spatial variability within ductal carcinoma in situ (DCIS) samples and its association with progression are not well understood.
To characterise tissue spatial architecture and the microenvironment of DCIS, we designed and validated a new deep learning pipeline, UNMaSk. Following automated detection of single DCIS ducts using a new method IM-Net, we applied spatial tessellation to create virtual boundaries for each duct. To study local TIL infiltration for each duct, DRDIN was developed for mapping the distribution of TILs. In a dataset comprising grade 2-3 pure DCIS and DCIS adjacent to invasive cancer (adjacent DCIS), we found that pure DCIS cases had more TILs compared to adjacent DCIS. However, the colocalisation of TILs with DCIS ducts was significantly lower in pure DCIS compared with adjacent DCIS, which may suggest a more inflamed tissue ecology local to DCIS ducts present in adjacent DCIS cases.
Our study demonstrates that technological developments in deep convolutional neural networks and digital pathology can enable automated morphological and microenvironmental analysis of
DCIS, providing a new way to study differential immune ecology for individual ducts and identify new markers of progression.

Item Type: Journal Article
Subjects: Q Science > QA Mathematics > QA76 Electronic computers. Computer science. Computer software
Q Science > QR Microbiology
R Medicine > RC Internal medicine
Divisions: Faculty of Science > Computer Science
Library of Congress Subject Headings (LCSH): Breast -- Cancer, Microbial ecology, Tumors, Lymphocytes
Journal or Publication Title: npj Breast Cancer
Publisher: Springer
ISSN: 2374-4677
Official Date: 2021
Dates:
DateEvent
2021Published
1 March 2021Available
21 October 2020Accepted
Volume: 7
Article Number: 19
DOI: 10.1038/s41523-020-00205-5
Status: Peer Reviewed
Publication Status: Published
Access rights to Published version: Open Access
RIOXX Funder/Project Grant:
Project/Grant IDRIOXX Funder NameFunder ID
2015NovPR638Breast Cancer Nowhttp://dx.doi.org/10.13039/100009794
R01 CA185138National Institutes of Healthhttp://dx.doi.org/10.13039/100000002
BC132057Congressionally Directed Medical Research Programshttp://dx.doi.org/10.13039/100000090
CRUK C45982/A21808Cancer Research UKhttp://dx.doi.org/10.13039/501100000289
C9203/A28770Cancer Research UKhttp://dx.doi.org/10.13039/501100000289
C25858/A28592Cancer Research UKhttp://dx.doi.org/10.13039/501100000289
A2714Rosetrees Trusthttp://dx.doi.org/10.13039/501100000833
CCLGA201906Children's Cancer and Leukaemia Grouphttp://dx.doi.org/10.13039/100011692
U54 CA217376 National Institutes of Healthhttp://dx.doi.org/10.13039/100000002
H2020-MSCA-ITN-2019European Commissionhttp://dx.doi.org/10.13039/501100000780
UNSPECIFIEDNIHR Biomedical Research Centre, Royal Marsden NHS Foundation Trust/Institute of Cancer Researchhttp://dx.doi.org/10.13039/100014461
U54 CA217376 National Institutes of Healthhttp://dx.doi.org/10.13039/100000002
U2C CA233254National Institutes of Healthhttp://dx.doi.org/10.13039/100000002
P01 CA91955National Institutes of Healthhttp://dx.doi.org/10.13039/100000002
R01 CA170595National Institutes of Healthhttp://dx.doi.org/10.13039/100000002
R01 CA185138National Institutes of Healthhttp://dx.doi.org/10.13039/100000002
R01 CA140657National Institutes of Healthhttp://dx.doi.org/10.13039/100000002
BC132057Congressionally Directed Medical Research Programshttp://dx.doi.org/10.13039/100000090
ADHS18-198847Arizona Biomedical Research Commissionhttp://dx.doi.org/10.13039/100008335
U2C CA17035National Institutes of Healthhttp://dx.doi.org/10.13039/100000002
R01 CA170595National Institutes of Healthhttp://dx.doi.org/10.13039/100000002
R01 CA185138National Institutes of Healthhttp://dx.doi.org/10.13039/100000002
BC132057Congressionally Directed Medical Research Programshttp://dx.doi.org/10.13039/100000090
Grand Challenge AwardCancer Research UKhttp://dx.doi.org/10.13039/501100000289
UO1 CA214183National Institutes of Healthhttp://dx.doi.org/10.13039/100000002
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