Data basic properties and analysis overview. A, Distribution, annotation, and cell fractions of 12 major immune cell types in matched tumor-PBMC CD45+ scRNA-seq data from 26 patients with treatment-naïve HNSCC. B, A volcano plot showing differential fractions of abundance of 12 major immune cell types between tumor tissues and PBMCs. C, Significantly differentially expressed genes in 12 annotated immune cell types from tumor tissues and PBMCs. D, An overview of the study: First, (1) the ICFs and (2) the gene expression levels of major immune cell types in the TME are predicted from the blood scRNA-seq data. Then, (3) immune signatures are identified from immune information in the blood and in the TME (which is predicted from the blood) to predict patients’ ICB response. FPR, false-positive rate; TPR, true-positive rate.
ARTICLE ABSTRACT
In this study, we explore the possibility of inferring characteristics of the tumor immune microenvironment from the blood. Specifically, we investigate two datasets of patients with head and neck squamous cell carcinoma with matched single-cell RNA sequencing (scRNA-seq) from peripheral blood mononuclear cells (PBMCs) and tumor tissues. Our analysis shows that the immune cell fractions and gene expression profiles of various immune cells within the tumor microenvironment can be inferred from the matched PBMC scRNA-seq data. We find that the established exhausted T-cell signature can be predicted from the blood and serve as a valuable prognostic blood biomarker of immunotherapy response. Additionally, our study reveals that the inferred ratio between tumor memory B- and regulatory T-cell fractions is predictive of immunotherapy response and is superior to the well-established cytolytic and exhausted T-cell signatures. These results highlight the promising potential of PBMC scRNA-seq in cancer immunotherapy and warrant, and will hopefully facilitate, further investigations on a larger scale. The code for predicting tumor immune microenvironment from PBMC scRNA-seq, TIMEP, is provided, offering other researchers the opportunity to investigate its prospective applications in various other indications.
Our work offers a new and promising paradigm in liquid biopsies to unlock the power of blood single-cell transcriptomics in cancer immunotherapy.
