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Spatial immune profiling of the colorectal tumor microenvironment predicts good outcome in stage II patients

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Nearchou_2020_npjDM_Spatialimmune_CC.pdf (2.481Mb)
Date
15/05/2020
Author
Nearchou, Ines P.
Gwyther, Bethany M.
Georgiakakis, Elena C. T.
Gavriel, Christos
Lillard, Kate
Kajiwara, Yoshiki
Ueno, Hideki
Harrison, David James
Caie, Peter David
Keywords
Colorectal cancer
Image analysis
Tumor microenvironment
Prognosis
Digital pathology
RC0254 Neoplasms. Tumors. Oncology (including Cancer)
RB Pathology
QA76 Computer software
NDAS
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Abstract
Cellular subpopulations within the colorectal tumor microenvironment (TME) include CD3+ and CD8+ lymphocytes, CD68+ and CD163+ macrophages, and tumor buds (TBs), all of which have known prognostic significance in stage II colorectal cancer. However, the prognostic relevance of their spatial interactions remains unknown. Here, by applying automated image analysis and machine learning approaches, we evaluate the prognostic significance of these cellular subpopulations and their spatial interactions. Resultant data, from a training cohort retrospectively collated from Edinburgh, UK hospitals (n = 113), were used to create a combinatorial prognostic model, which identified a subpopulation of patients who exhibit 100% survival over a 5-year follow-up period. The combinatorial model integrated lymphocytic infiltration, the number of lymphocytes within 50-μm proximity to TBs, and the CD68+/CD163+ macrophage ratio. This finding was confirmed on an independent validation cohort, which included patients treated in Japan and Scotland (n = 117). This work shows that by analyzing multiple cellular subpopulations from the complex TME, it is possible to identify patients for whom surgical resection alone may be curative.
Citation
Nearchou , I P , Gwyther , B M , Georgiakakis , E C T , Gavriel , C , Lillard , K , Kajiwara , Y , Ueno , H , Harrison , D J & Caie , P D 2020 , ' Spatial immune profiling of the colorectal tumor microenvironment predicts good outcome in stage II patients ' , npj Digital Medicine , vol. 3 , 71 . https://doi.org/10.1038/s41746-020-0275-x
Publication
npj Digital Medicine
Status
Peer reviewed
DOI
https://doi.org/10.1038/s41746-020-0275-x
ISSN
2398-6352
Type
Journal article
Rights
Copyright © The Author(s) 2020. Open Access. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Description
This study was funded by Medical Research Scotland and Indica Labs, Inc., who also provided in-kind resource.
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  • University of St Andrews Research
URI
http://hdl.handle.net/10023/19977

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