Fig. 1: Predictive performance of transcriptome signatures and PD-1 inhibitor response heterogeneity.

a Details of the 94 melanoma biopsies analyzed in this study, including 53 pre-treatment (PRE) and 41 on-treatment samples. Of the 53 pre-treatment tumor specimens analyzed, 31 were obtained from patients who subsequently underwent complete response (CR) or partial response (PR) by irRC criteria and 22 pre-treatment biopsies were obtained from patients who had stable disease (SD) or progressive disease (PD) by irRC. b Venn diagram showing the 68 patients included in this study and the distribution of pre-treatment, responding and progressing tumor specimens (n = 94). c Immune-predictive transcriptome scores derived for each PRE-treatment melanoma biopsy (n = 44) and patient response data were used to generate receiver operator characteristic (ROC) curves measuring the performance of each indicated signature in predicting PD-1 inhibitor responses in our patient cohort. The resulting AUCs and p values are tabulated. The signatures applied to our dataset were derived from the following references: IPRES signature¹⁷, IMPRES signature²¹, CD8A/CSF1R ratio¹⁵, 18-immune gene set¹⁸, TIDE²², CYT score²⁴ and CIBERSORT estimated relative proportion of CD8+ T cells⁷⁴ (see Supplementary Data 6). d CT scans from patient 45. Tumor metastases pre-treatment and on PD-1 inhibitor therapy (week 12 and 24) measured by CT images are shown. Regions of interest in CT images are circled in red. Top images show new lesion at week 12 that continued growing in size at week 24. Middle images show core biopsied lesion that underwent partial response. Lower images show pre-existing lesion that initially responded at week 12 but progressed by week 24. e CT scans from patient 49. Regions of interest in CT images are circled in red, and show partial response of large, inflamed pre-treatment inguinal LN metastasis (upper images) and the appearance of a new, subcutaneous buttock metastasis on treatment (week 8; lower images). Despite excision of the new metastasis, there were multiple new metastases in bone and lymph node on second restaging. Scale bar is shown.