Single cell analysis of pan-cancer tumor microenvironment in immunotherapy

Hum Mol Genet. 2025 Jun 19:ddaf101. doi: 10.1093/hmg/ddaf101. Online ahead of print.

Abstract

The high heterogeneity of tumor microenvironment (TME) is a key factor affecting immunotherapy. We integrated immunotherapy related scRNA-seq and bulk datasets to analyze the TME, mine key factors and dissect the mechanism in immunotherapy. Analyzing the cell composition of TME in cancer immunotherapy, we revealed key TME cell types, including B cells, CD8+ T cells and fibroblasts. Through cell subsets identification, pseudo-time sequence and functional status analysis of malignant cells, it was found that the functional status of malignant cell was heterogeneous under different immunotherapy conditions. Key cellular interactions in cancer immunotherapy were also revealed. Further, 16 marker genes and 6 marker cell types of cancer immunotherapy were identified, and then gene and cell model were constructed to predict the immunotherapy response of individuals, and the model were evaluated based on multiple independent validation datasets. This study can provide important guidance for improving the efficiency and understanding the mechanism of cancer immunotherapy.

Keywords: biomarker; cancer immunotherapy; scRNA-seq; tumor microenvironment.