Fig. 4

The landscape of heterogeneity of neoantigen depletion. A Change in the number of nonsynonymous binder SNVs (predicted in silico) and nonsynonymous non-binder SNVs compared to pre-treatment. Reduction in only putative neoantigens illustrates selective pressure and immunoediting. One sample Wilcox test P (compared to zero) is shown. B Clonality of neoantigen depletion. Only strong binders are shown. C Association between neoantigen depletion and ITH subtypes. D, E Immunoediting in an HLA-intact patient NIVO20 through reduced neoantigen expression. NKA/NKB/NKC (shown in RED) are normal adjacent tissues 1, 2, and 4 cm away from the center of the tumor; BX (shown in blue) represents pre-treatment biopsy; RA/RB/RC/RD/RE (shown in green) illustrate 5 tumor regions from the treated tumor sample. F Immunoediting with amino acid resolution. Higher phenylalanine (F) depletion compared to glutamic acid (E) and arginine (R) suggests immune selection. G Association between putative neoantigen depletion and myeloid activation across all regions of patients where pre-treatment WES data was available (n = 16 patients). H Association between the fraction of expressed putative neoantigens depleted and immune signatures. In H, correlations are calculated across different regions of the same patient, for all patients with > 3 treated, as well as pre-treatment RNA samples were available (n = 7 patients). I, J HERVs are enriched in tumors compared to normal samples and are associated with treatment. K HERV depletion association with myeloid signature. L Clonotype tracking of dominant untreated T cell clones in treated regions of patient NIVO20. The color of each ribbon shows different T cell clones, and the width is scaled corresponding to the frequency of that clone. Tissue data consists of 5 tumor regions after treatment (RA/RB/RC/RD/RE), one single normal adjacent (NKC), and one tumor region pre-treatment (BX). Likewise, PBMC data points on treatment are NIVO20-68, -54, -40, -12. M, N TCR diversity is negatively associated with neoantigen depletion and HLA LOH