Combined Assessment of the Tumor-Stroma Ratio and Tumor Immune Cell Infiltrate for Immune Checkpoint Inhibitor Therapy Response Prediction in Colon Cancer.
Cells
; 10(11)2021 10 28.
Article
em En
| MEDLINE
| ID: mdl-34831157
ABSTRACT
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 (p = 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.
Palavras-chave
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Linfócitos do Interstício Tumoral
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Neoplasias do Colo
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Inibidores de Checkpoint Imunológico
Tipo de estudo:
Etiology_studies
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Incidence_studies
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Observational_studies
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Prognostic_studies
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Risk_factors_studies
Limite:
Humans
Idioma:
En
Revista:
Cells
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Holanda