a. The proposed immune classification imposed on density plot showing distribution of lymphocyte percentage. The middle zone corresponds to the intermediate phenotype, red zone for immune hot and blue zone for immune cold. Black dash line shows the median. This classification was validated after applying small perturbations to the thresholds to reclassify regional immune phenotypes, illustrated as grey dash lines: no intermediate zone (i.e. hard median for separating hot and cold), standard deviation (SD)/2 above and below the median, SD/3 and SD/6. b. Forest plots to show repeated multivariate Cox regression tests for the number of immune cold regions using these new classifications (= 79 patients), after accounting for stage, total number of samples, upper quartile of clonal neoantigens determined for LUAD and LUSC individually, and other clinical parameters. Box plots showing difference in genomic distance for pairs of hot regions compared with pairs of cold regions for LUAD and LUSC separately (LUAD: = 45 hot pairs, 45 cold pairs for no intermediate zone; = 19 hot, 25 cold for SD/2; = 25 hot, 33 cold for SD/3; = 32 hot, 41 cold for SD/6. LUSC: = 32 hot pairs, 54 cold pairs for no intermediate zone; = 19 hot, 27 cold for SD/2; = 19 hot, 37 cold for SD/3; = 27 hot, 41 cold for SD/6.). c. Box plots showing significant difference in CD8+ RNA-seq signature using the Danaher method between regions of hot and cold phenotype across all classification schemes (= 219 for SD/4; 275 for no intermediate zone; 173 for SD/2; 204 for SD/3; 237 for SD/6). d. Distribution and difference of lymphocytic infiltration for LUAD versus LUSC regions in TRACERx (= 275 regions; 85 patients) as well as distribution for LUAD in LATTICe-A (= 4,324 samples; 970 patients). Horizontal lines in the distribution plots indicate mean values. For statistical comparisons among groups, a two-sided, non-parametric, unpaired, Wilcoxon signed-rank test was used, unless stated otherwise.