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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| Format: | Article |
| Language: | English |
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MDPI AG
2021-10-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/10/11/2935 |
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| 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 |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-03-10T05:37:44Z |
| format | Article |
| id | doaj.art-c66082d9b5ab40fd8accba08e8ab3f4b |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-10T05:37:44Z |
| publishDate | 2021-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-c66082d9b5ab40fd8accba08e8ab3f4b2023-11-22T22:48:54ZengMDPI AGCells2073-44092021-10-011011293510.3390/cells10112935Combined Assessment of the Tumor–Stroma Ratio and Tumor Immune Cell Infiltrate for Immune Checkpoint Inhibitor Therapy Response Prediction in Colon CancerCor J. Ravensbergen0Meaghan Polack1Jessica Roelands2Stijn Crobach3Hein Putter4Hans Gelderblom5Rob A. E. M. Tollenaar6Wilma E. Mesker7Department of Surgery, Leiden University Medical Center, Albinusdreef 2, 2300RC Leiden, The NetherlandsDepartment of Surgery, Leiden University Medical Center, Albinusdreef 2, 2300RC Leiden, The NetherlandsDepartment of Pathology, Leiden University Medical Center, Albinusdreef 2, 2300RC Leiden, The NetherlandsDepartment of Pathology, Leiden University Medical Center, Albinusdreef 2, 2300RC Leiden, The NetherlandsDepartment of Medical Statistics, Leiden University Medical Center, Albinusdreef 2, 2300RC Leiden, The NetherlandsDepartment of Medical Oncology, Leiden University Medical Center, Albinusdreef 2, 2300RC Leiden, The NetherlandsDepartment of Surgery, Leiden University Medical Center, Albinusdreef 2, 2300RC Leiden, The NetherlandsDepartment of Surgery, Leiden University Medical Center, Albinusdreef 2, 2300RC Leiden, The NetherlandsThe 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.https://www.mdpi.com/2073-4409/10/11/2935tumor–stroma ratiocolon cancertumor-infiltrating immune cellsimmunotherapytumor microenvironmentcheckpoint inhibitor |
| spellingShingle | 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 Cells tumor–stroma ratio colon cancer tumor-infiltrating immune cells immunotherapy tumor microenvironment checkpoint inhibitor |
| title | 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_short | 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 |
| topic | tumor–stroma ratio colon cancer tumor-infiltrating immune cells immunotherapy tumor microenvironment checkpoint inhibitor |
| url | https://www.mdpi.com/2073-4409/10/11/2935 |
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