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Peer-reviewedCC BY 4.0International Journal of Genomics

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

  1. 1Department of Radiology People′s Hospital of Chongqing Liangping District Chongqing China

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.

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BibTeX
@article{mao2026tumor,
  title = {{Tumor Immune Microenvironment Heterogeneity and Key Immunoregulatory Gene Expression in Lung Cancer}},
  author = {Jianghua Mao and Xue Zhang and Rongwei Yang and Xiaolin Wang},
  journal = {International Journal of Genomics},
  year = {2026},
  month = nov,
  doi = {10.1155/ijog/8365959},
  url = {https://doi.org/10.1155/ijog/8365959},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Tumor Immune Microenvironment Heterogeneity and Key Immunoregulatory Gene Expression in Lung Cancer
AU  - Jianghua Mao
AU  - Xue Zhang
AU  - Rongwei Yang
AU  - Xiaolin Wang
PY  - 2026
DA  - 2026/11/02
JO  - International Journal of Genomics
DO  - 10.1155/ijog/8365959
UR  - https://doi.org/10.1155/ijog/8365959
AB  - 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.
SN  - 2314-436X
SN  - 2314-4378
ER  -