Tumor Immune Microenvironment Heterogeneity and Key Immunoregulatory Gene Expression in Lung Cancer
Jianghua Mao, Xue Zhang, Rongwei Yang, Xiaolin WangBackground
The aim of this study is to characterize the cellular heterogeneity and key immunoregulatory gene expression patterns of the tumor immune microenvironment (TIME) in lung cancer using single‐cell RNA sequencing (scRNA‐seq).
Methods
The scRNA‐seq dataset GSM4453577 was retrieved from NCBI GEO. Unsupervised clustering, cell–cell communication analysis, pseudotime trajectory reconstruction, and GO/KEGG enrichment analyses were performed.
Results
Seven immune cell types were annotated from 223 single cells after quality control. Macrophages demonstrated the strongest outgoing intercellular interaction intensity and showed relatively high SPP1‐associated expression‐based interaction scores, with macrophages and monocytes identified as the dominant SPP1 signal sources. ISG15 showed the broadest expression across all seven immune cell types (highest z‐scores in stem‐like/mast cells and neutrophils), whereas TNFRSF18 and TNFRSF4 exhibited similar descriptive expression trends during intermediate pseudotime stages (scaled 0–1), with TNFRSF18 enriched in stem‐like/mast cells ( z = 1.93) and TNFRSF4 in mast cells ( z = 2.22). T cell, NK cell, and Treg markers (CD3E, NKG7, and FOXP3) were below the detection threshold, consistent with the predominantly myeloid/B‐lineage immune infiltrate in this sample.
Conclusion
ScRNA‐seq analysis of a single GEO sample (GSM4453577; 223 cells; PC1 explaining 5.3% of variance) suggested myeloid/B‐lineage immune cell heterogeneity in the lung cancer microenvironment and identified ISG15, TNFRSF18, and TNFRSF4 as candidates of potential immunoregulatory interest; external multisample validation is required before generalizing these findings.