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Tumor Immune Microenvironment Heterogeneity and Key Immunoregulatory Gene Expression in Lung Cancer

Year: 2026
Type: article
Abstract: Background 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.
DOI: 10.1155/ijog/8365959
Language: English
Open Access status: gold
Estimated APC paid: $2,380
OpenAlex ID: W7225195164
FWCI:
Cites: 19
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Related to: 10