PD-1 Blockade in Chinese versus Western Patients with Melanoma

Abstract

In this trial of programmed cell death-1 (PD-1) blockade with toripalimab in previously treated Chinese patients with melanoma, unique histologic and molecular features may explain why the objective response rate is lower than those defined in Western populations. This work suggests future avenues for investigating mechanisms of melanoma formation and resistance to PD-1 blockade.See related article by Tang et al., p. 4250.

Figure 1.. Clinically relevant somatic mutations and immune gene expression in melanoma.

(A) 98 pre-treatment tumor samples from Tang et al. (1). Data were provided via direct communication with the authors. Panels shown (from top to bottom): tumor mutational burden (TMB), defined as total number of somatic mutations predicted to alter amino acids in protein sequences, with categories shown in the legend; somatic mutations in 20 individual genes representative of MAPK signaling and others, with samples shown on the column and genes on the row with % altered in between parentheses; demographic and clinical annotation bars showing gender, melanoma subtype, IRC ORR and INV ORR; GEP immune expression signature (3) shown as the ssGSEA scores in individual samples; expression heatmap of 18 genes from the GEP signature. Samples were presorted on column, first by subtype and then by GEP score lower to higher within each subtype. 39 samples with RNAseq data available are shown in the heatmap, others missing are shown as grey. (B) 144 pre-treatment samples from Liu et al. (4). Data were from the published supplementary tables of the study. Panels shown are the same as in A. Demographic and clinical annotation bars showing gender, subtype, prior therapy (naïve to immune-checkpoint blockade or not), and BORR. In the expression heatmap, 17 genes are shown, CCL5 was not present in the RNAseq expression matrix from the original study, hence not shown. 121 samples with RNAseq data available are shown. ssGSEA was performed using Bioconductor package GSVA (v1.32.0). IRC ORR = independent review committee assessed ORR. INV ORR = investigator assessed ORR. BORR = best overall response rate. GEP = gene expression profile. ssGSEA = single-sample Gene Set Enrichment Analysis.