Fig. 1. Anti-PD-1 therapy elicits durable responses in BRAF-driven murine melanoma.
a Schematic representation of the timeline relative to our mouse melanoma model. Melanoma developed in mice a few months after the induction of oncogenic BRAFV600E and exposure to ultraviolet radiation (UVR). When tumors reached ~100 mm3, mice were randomized to receive anti-PD-1 antibody or IgG. m, months. b Growth curves and photographs at indicated treatment times of a representative mouse exposed to UVR and bearing two tumors (T1 and T2) with differential response to PD-1 blockade. c Cartoon depicting our refined experimental approach. UVR exposure was limited to ~1 cm2, and a pre-treatment biopsy was collected from established tumors (~100 mm3). d Kaplan–Meier curves showing survival of mice bearing single tumors treated with anti-PD-1 (n = 38 animals) or IgG (n = 21 animals). Two-sided log-rank test was performed to determine statistical difference between the survival curves. e Tumor growth curves from animals treated with anti-PD-1 (continuous green/orange/purple lines, n = 53 tumors) or IgG (dashed black lines, n = 19 tumors) defines three cohorts: DR durable response (green, n = 13 tumors), SR short-lived response (purple, n = 6 tumors), NR nonresponders (orange, n = 34 tumors). Line, single tumor. f Changes in non-synonymous single-nucleotide variant (nsSNV) numbers in paired pre- and on-treatment mouse samples from DR (n = 7 tumors) and NR (n = 6 tumors). Two-tailed Wilcoxon test was performed to determine statistical difference between matched pre- and on-treatment samples, two-tailed Mann–Whitney U test was performed to determine statistical difference between DR and NR groups in pre- or on-treatment samples. Dot, single tumor; line, paired samples; ns, not significant.