Fig. 5: Increasing immune escape during neoadjuvant treatment correlates with poor treatment response.
a–d, Violins showing the neoantigenic mutational burden during neoadjuvant treatment in all samples (a), stratified by treatment response (b), expressed as a proportion of total SNVs (c) and stratified by clonality (d). Clonal and subclonal neoantigenic mutational burden during neoadjuvant treatment. Mutations of each sample were classified as clonal or subclonal based on the copy number (CN) and cellularity-adjusted CCF. e, Distribution of neoantigenic SNVs based on their copy number states. The CN-normalized proportion of neoantigenic SNVs in each CN segment was calculated. f, Expression of neoantigens during treatment. g,h, Neoantigen expression in EAC according to immune infiltration score for CD8+ T cells (g) and CD4+ T cells (h). i, Presence of HLA-LOH, PD-L1 overexpression and B2M mutations in individual samples from NRPs (left) and REPs (right). Samples from individual patients are separated by vertical black lines. PD-L1 overexpression was defined as PD-L1 expression >2 s.d. from the mean of all treatment-naive samples. j, Proportion of early and late occurrence of genetic and nongenetic immune escape in cohort of n = 27 patients. Genetic immune escape refers to mutations or LOH in HLA or B2M mutations, whereas PD-L1 overexpression represents transcriptomic immune escape. P value calculated by the two-sided chi-squared test (P = 0.003). k, PD-L1 expression during neoadjuvant treatment. l, Proportion of immune escaped samples and their escape mechanism stratified by treatment response in NRPs (n = 17 samples) and REPs (n = 47 samples) with matching WES and RNA-seq data. m, Proportion of samples with HLA-LOH stratified by treatment response in NRPs (n = 22 samples) and REPs (n = 48 samples). P values in j–m are calculated by the two-sided chi-squared test. P values in all other panels are calculated by a two-sided Wilcoxon test, unless stated otherwise. Amplif., amplification; I.E., immune escape; overexpr., overexpression.
