Fig. 2

Chemoimmunotherapy enhances cellular metabolism in malignant cells and induces an immunosuppressive microenvironment in normal epithelial cells. A t-SNE maps showing the distribution of epithelial cells in each sample and the distribution of different epithelial subtypes. B Heatmap showing the marker genes used for identification. C Bar plot showing the proportions of epithelial subtypes in each sample and group. LUAD: lung adenocarcinoma; LUSC: lung squamous cell carcinoma. D Clustering of the epithelial cells from all samples into aneuploid cells and diploid cells and t-SNE maps showing the distribution of epithelial cells in the TN and PT groups. E Bar plot (left) and heatmap (right) showing the fraction of each epithelial cell type in tumor cells and normal epithelial cells. F Volcano map showing the differentially expressed genes (DEGs) of tumor cells between TNs and PTs, and the top 10 DEGs are labeled. G Bar plot showing the significantly enriched pathways in malignant cells before and after chemoimmunotherapy. Bars in blue color indicate the enriched pathways after treatment, and bars in green indicate the enriched pathways before treatment. The pathways are ranked by GSVA score. Red arrows indicate the pathways selected for experimental validation. H Images from IHC staining for the clinical sample sections from five NSCLC patients. The detected proteins were labled on the top of the panel, and the number of patients with treatment information /pathological assessment were labeled on the left of the panel. Scale bar = 30 μM, magnificent = 400 X. I, J The spatial localizations of tumor cells, normal epithelial cells and other cell types were annotated in NSCLC sections via the RCTD algorithm, and the percentage of each cell type is shown in a bar plot. The tumor boundaries in tumor-3 were marked in yellow, and the boundaries of transition zone were marked in green. The areas of TLSs in tumor-2 were labeled by yellow dot lines. K Neighboring analysis of the spatial distance between all cell types. Within the white dotted line are pairs of cell types that show significant changes in spatial distance with increasing sensitivity to chemoimmunotherapy