Extended Data Fig. 6: HLA-I promiscuity is a major determinant of patient survival.

a, Carrying a single promiscuous HLA-I allele has no impact on survival. The patients in Fig. 1a to c were classified based on the number of promiscuous alleles in their genotypes. Alleles with promiscuity levels in the top quartile were considered to be promiscuous. Two-sided log-rank test P values are shown. In the second analysis, between-group differences were also tested for trend (see Methods). The vertical axes indicate the probability of survival. b, HLA alleles belonging to the B44 supergroup have low promiscuity. B44 alleles are highlighted in blue and have significantly lower promiscuity than alleles not belonging to this group (two-sided Wilcoxon’s rank-sum test P: 0.049). c-e, No significant association between HLA-I genotype Pr and (c) HLA homozygosity, (d) HLA-I evolutionary divergence (HED), (e) mutational burden. All patients from Fig. 3a to c were included in these analyses. c, There was no significant difference in genotype Pr between fully HLA heterozygous patients (n = 251) and the ones homozygous for at least one HLA-I locus (n = 65 patients). The P value for a two-sided Wilcoxon’s rank-sum test is indicated. Similarly, there was no significant association between (d) genotype Pr and mean HED (Spearman’s ρ: −0.02, two-sided correlation test P = 0.77, n = 316 patients) and (e) genotype Pr and tumor mutational burden of cancer immunotherapy patients (Spearman’s ρ: 0.02, two-sided correlation test P = 0.77, n = 316 patients). Dashed red lines indicate a smooth curve fitted using the cubic smoothing spline method in R (see Methods). On the boxplot, horizontal lines indicate median, boxes indicate the interquartile range (IQR), vertical lines indicate 1^st quartile - 1.5 × IQR and 3^rd quartile + 1.5 × IQR.