iBRIDGE: A Data Integration Method to Identify Inflamed Tumors from Single-cell RNA-Seq Data and Differentiate Cell Type-Specific Markers of Immune-Cell Infiltration.
Cancer Immunol Res
; 11(6): 732-746, 2023 06 02.
Article
en En
| MEDLINE
| ID: mdl-37023414
ABSTRACT
The development of immune checkpoint-based immunotherapies has been a major advancement in the treatment of cancer, with a subset of patients exhibiting durable clinical responses. A predictive biomarker for immunotherapy response is the preexisting T-cell infiltration in the tumor immune microenvironment (TIME). Bulk transcriptomics-based approaches can quantify the degree of T-cell infiltration using deconvolution methods and identify additional markers of inflamed/cold cancers at the bulk level. However, bulk techniques are unable to identify biomarkers of individual cell types. Although single-cell RNA sequencing (scRNA-seq) assays are now being used to profile the TIME, to our knowledge there is no method of identifying patients with a T-cell inflamed TIME from scRNA-seq data. Here, we describe a method, iBRIDGE, which integrates reference bulk RNA-seq data with the malignant subset of scRNA-seq datasets to identify patients with a T-cell inflamed TIME. Using two datasets with matched bulk data, we show iBRIDGE results correlated highly with bulk assessments (0.85 and 0.9 correlation coefficients). Using iBRIDGE, we identified markers of inflamed phenotypes in malignant cells, myeloid cells, and fibroblasts, establishing type I and type II interferon pathways as dominant signals, especially in malignant and myeloid cells, and finding the TGFß-driven mesenchymal phenotype not only in fibroblasts but also in malignant cells. Besides relative classification, per-patient average iBRIDGE scores and independent RNAScope quantifications were used for threshold-based absolute classification. Moreover, iBRIDGE can be applied to in vitro grown cancer cell lines and can identify the cell lines that are adapted from inflamed/cold patient tumors.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Análisis de Expresión Génica de una Sola Célula
/
Neoplasias
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
Cancer Immunol Res
Año:
2023
Tipo del documento:
Article