细胞类型特异性基因特征揭示了肺癌中新的免疫检查点和预后标志物

The tumor microenvironment (TME) is a complex interplay of immune, stromal, and malignant cells whose interactions shape cancer progression and therapeutic responses. In this study, we performed an integrative single-cell transcriptomic analysis to define cell-type-specific gene signatures with emphasis on immune-tumor communication, exhaustion states, and their prognostic implications.

We derived 30-gene signatures for B cells, CD8⁺ T cells, fibroblasts, macrophages, NK cells, T cells, Tregs, tumor cells, and unclassified clusters. Ligand-receptor mapping revealed widespread communication, including macrophage-fibroblast and Treg-tumor axes. Pseudotime analysis further showed immune exhaustion as a dynamic process enriched with checkpoint genes such as PDCD1, CTLA4, LAG3, and TIGIT, particularly within Tregs and exhausted CD8⁺ T cells.

Survival analysis of representative genes revealed contrasting effects of immune and stromal activity: MS4A1 (B-cell signature) and TPPP3 (tumor signature) correlated with improved prognosis, whereas fibroblast-specific COL1A1 predicted poor outcomes. Incorporation of less-characterized genes highlighted novel prognostic signals. Correlation networks among signatures underscored the functional interdependence of immune and stromal compartments.

Together, this study provides a systems-level framework linking transcriptional with survival outcomes. By combining established immune checkpoints with novel candidates, our findings expand the biomarker landscape for prognostic stratification and therapeutic targeting in lung cancer.