Fig 1: Distinct immunological profiles of the four subtypes.a Heatmap depicting the distribution of immune checkpoint genes among the four subtypes in the LC-1000 cohort. b Boxplots illustrating the expression levels of immune checkpoint genes, such as PD-L1, CTLA4, PDCD1 and CXCL9, across the four subtypes in the LC-1000 cohort. c Representative images of multiplex immunofluorescence staining for CD8+NK+PanCK+ cells in the IMD (left panel) and IME (right panel) subtypes. CD8+ T, NK and tumor cells were detected using CD8, CD16 and PanCK staining. DAPI was used to identify nucleated cells. Scale bars in both the main and magnified images correspond to 100 μm. d Boxplot illustrating the comparison of CD8+, NK and PanCK cell density (%) and area (%) between the IMD and IME subtypes. e Comparison and distribution of gene mutation frequencies between IMD (characterized by the coldest immune cell profile) and IME (characterized by the hottest immune cell profile). f Progression-free survival was analyzed for mutant and wild-type DYNC2H1, whose frequency was significantly higher in IME than in IMD, among the 91 patients who received immunotherapy. *P < 0.05, **P < 0.01, and ***P < 0.001.