Combined Assessment of the Tumor–Stroma Ratio and Tumor Immune Cell Infiltrate for Immune Checkpoint Inhibitor Therapy Response Prediction in Colon Cancer

The best current biomarker strategies for predicting response to immune checkpoint inhibitor (ICI) therapy fail to account for interpatient variability in response rates. The histologic tumor–stroma ratio (TSR) quantifies intratumoral stromal content and was recently found to be predictive of respon...

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Autores principales:	Cor J. Ravensbergen, Meaghan Polack, Jessica Roelands, Stijn Crobach, Hein Putter, Hans Gelderblom, Rob A. E. M. Tollenaar, Wilma E. Mesker
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	tumor–stroma ratio colon cancer tumor-infiltrating immune cells immunotherapy tumor microenvironment checkpoint inhibitor Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/c66082d9b5ab40fd8accba08e8ab3f4b
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spelling	oai:doaj.org-article:c66082d9b5ab40fd8accba08e8ab3f4b2021-11-25T17:09:14ZCombined Assessment of the Tumor–Stroma Ratio and Tumor Immune Cell Infiltrate for Immune Checkpoint Inhibitor Therapy Response Prediction in Colon Cancer10.3390/cells101129352073-4409https://doaj.org/article/c66082d9b5ab40fd8accba08e8ab3f4b2021-10-01T00:00:00Zhttps://www.mdpi.com/2073-4409/10/11/2935https://doaj.org/toc/2073-4409The best current biomarker strategies for predicting response to immune checkpoint inhibitor (ICI) therapy fail to account for interpatient variability in response rates. The histologic tumor–stroma ratio (TSR) quantifies intratumoral stromal content and was recently found to be predictive of response to neoadjuvant therapy in multiple cancer types. In the current work, we predicted the likelihood of ICI therapy responsivity of 335 therapy-naive colon adenocarcinoma tumors from The Cancer Genome Atlas, using bioinformatics approaches. The TSR was scored on diagnostic tissue slides, and tumor-infiltrating immune cells (TIICs) were inferred from transcriptomic data. Tumors with high stromal content demonstrated increased T regulatory cell infiltration (<i>p</i> = 0.014) but failed to predict ICI therapy response. Consequently, we devised a hybrid tumor microenvironment classification of four stromal categories, based on histological stromal content and transcriptomic-deconvoluted immune cell infiltration, which was associated with previously established transcriptomic and genomic biomarkers for ICI therapy response. By integrating these biomarkers, stroma-low/immune-high tumors were predicted to be most responsive to ICI therapy. The framework described here provides evidence for expansion of current histological TIIC quantification to include the TSR as a novel, easy-to-use biomarker for the prediction of ICI therapy response.Cor J. RavensbergenMeaghan PolackJessica RoelandsStijn CrobachHein PutterHans GelderblomRob A. E. M. TollenaarWilma E. MeskerMDPI AGarticletumor–stroma ratiocolon cancertumor-infiltrating immune cellsimmunotherapytumor microenvironmentcheckpoint inhibitorBiology (General)QH301-705.5ENCells, Vol 10, Iss 2935, p 2935 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	tumor–stroma ratio colon cancer tumor-infiltrating immune cells immunotherapy tumor microenvironment checkpoint inhibitor Biology (General) QH301-705.5
spellingShingle	tumor–stroma ratio colon cancer tumor-infiltrating immune cells immunotherapy tumor microenvironment checkpoint inhibitor Biology (General) QH301-705.5 Cor J. Ravensbergen Meaghan Polack Jessica Roelands Stijn Crobach Hein Putter Hans Gelderblom Rob A. E. M. Tollenaar Wilma E. Mesker Combined Assessment of the Tumor–Stroma Ratio and Tumor Immune Cell Infiltrate for Immune Checkpoint Inhibitor Therapy Response Prediction in Colon Cancer
description	The best current biomarker strategies for predicting response to immune checkpoint inhibitor (ICI) therapy fail to account for interpatient variability in response rates. The histologic tumor–stroma ratio (TSR) quantifies intratumoral stromal content and was recently found to be predictive of response to neoadjuvant therapy in multiple cancer types. In the current work, we predicted the likelihood of ICI therapy responsivity of 335 therapy-naive colon adenocarcinoma tumors from The Cancer Genome Atlas, using bioinformatics approaches. The TSR was scored on diagnostic tissue slides, and tumor-infiltrating immune cells (TIICs) were inferred from transcriptomic data. Tumors with high stromal content demonstrated increased T regulatory cell infiltration (<i>p</i> = 0.014) but failed to predict ICI therapy response. Consequently, we devised a hybrid tumor microenvironment classification of four stromal categories, based on histological stromal content and transcriptomic-deconvoluted immune cell infiltration, which was associated with previously established transcriptomic and genomic biomarkers for ICI therapy response. By integrating these biomarkers, stroma-low/immune-high tumors were predicted to be most responsive to ICI therapy. The framework described here provides evidence for expansion of current histological TIIC quantification to include the TSR as a novel, easy-to-use biomarker for the prediction of ICI therapy response.
format	article
author	Cor J. Ravensbergen Meaghan Polack Jessica Roelands Stijn Crobach Hein Putter Hans Gelderblom Rob A. E. M. Tollenaar Wilma E. Mesker
author_facet	Cor J. Ravensbergen Meaghan Polack Jessica Roelands Stijn Crobach Hein Putter Hans Gelderblom Rob A. E. M. Tollenaar Wilma E. Mesker
author_sort	Cor J. Ravensbergen
title	Combined Assessment of the Tumor–Stroma Ratio and Tumor Immune Cell Infiltrate for Immune Checkpoint Inhibitor Therapy Response Prediction in Colon Cancer
title_short	Combined Assessment of the Tumor–Stroma Ratio and Tumor Immune Cell Infiltrate for Immune Checkpoint Inhibitor Therapy Response Prediction in Colon Cancer
title_full	Combined Assessment of the Tumor–Stroma Ratio and Tumor Immune Cell Infiltrate for Immune Checkpoint Inhibitor Therapy Response Prediction in Colon Cancer
title_fullStr	Combined Assessment of the Tumor–Stroma Ratio and Tumor Immune Cell Infiltrate for Immune Checkpoint Inhibitor Therapy Response Prediction in Colon Cancer
title_full_unstemmed	Combined Assessment of the Tumor–Stroma Ratio and Tumor Immune Cell Infiltrate for Immune Checkpoint Inhibitor Therapy Response Prediction in Colon Cancer
title_sort	combined assessment of the tumor–stroma ratio and tumor immune cell infiltrate for immune checkpoint inhibitor therapy response prediction in colon cancer
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/c66082d9b5ab40fd8accba08e8ab3f4b
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Combined Assessment of the Tumor–Stroma Ratio and Tumor Immune Cell Infiltrate for Immune Checkpoint Inhibitor Therapy Response Prediction in Colon Cancer

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