Prior anti-CTLA-4 therapy impacts molecular characteristics associated with anti-PD-1 response in advanced melanoma

• DOI: 10.1016/j.ccell.2023.03.010
• Publication Date: 2023-04-10T14:41:10Z
• Authors: Katie M. Campbell; Meelad Amouzgar; Shannon M. Pfeiffer; Timothy R. Howes; Egmidio Medina; Michael Travers; Gabriela Steiner; Jeffrey S. Weber; Jedd D. Wolchok; James Larkin; F. Stephen Hodi; Silvia Boffo; Lisa Salvador; Daniel Tenney; Tracy Tang; Marshall A. Thompson; Christine N. Spencer; Daniel K. Wells; Antoni Ribas
• Keywords: Immune checkpoint; CTLA-4

Immune checkpoint inhibitors (ICIs), including CTLA-4- and PD-1-blocking antibodies, can have profound effects on tumor immune cell infiltration that not been consistent in biopsy series reported to date. Here, we analyze seven molecular datasets of samples from patients with advanced melanoma (N = 514) treated ICI agents investigate clinical, genomic, transcriptomic features anti-PD-1 response cutaneous melanoma. We find prior anti-CTLA-4 therapy is associated differences individual gene, gene signatures responders. Anti-CTLA-4-experienced tumors respond PD-1 blockade exhibit increased mutational burden, inflammatory signatures, altered cycle processes compared anti-CTLA-4-naive or anti-CTLA-4-experienced, anti-PD-1-nonresponsive tumors. report a harmonized, aggregate resource suggest CTLA-4 marked the microenvironment impact predictive response.