Prior anti-CTLA-4 therapy impacts molecular characteristics associated with anti-PD-1 response in advanced melanoma Journal Article
| Authors: | Campbell, K. M.; Amouzgar, M.; Pfeiffer, S. M.; Howes, T. R.; Medina, E.; Travers, M.; Steiner, G.; Weber, J. S.; Wolchok, J. D.; Larkin, J.; Hodi, F. S.; Boffo, S.; Salvador, L.; Tenney, D.; Tang, T.; Thompson, M. A.; Spencer, C. N.; Wells, D. K.; Ribas, A. |
| Article Title: | Prior anti-CTLA-4 therapy impacts molecular characteristics associated with anti-PD-1 response in advanced melanoma |
| Abstract: | Immune checkpoint inhibitors (ICIs), including CTLA-4- and PD-1-blocking antibodies, can have profound effects on tumor immune cell infiltration that have 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 with ICI agents to investigate clinical, genomic, and transcriptomic features of anti-PD-1 response in cutaneous melanoma. We find that prior anti-CTLA-4 therapy is associated with differences in genomic, individual gene, and gene signatures in anti-PD-1 responders. Anti-CTLA-4-experienced melanoma tumors that respond to PD-1 blockade exhibit increased tumor mutational burden, inflammatory signatures, and altered cell cycle processes compared with anti-CTLA-4-naive tumors or anti-CTLA-4-experienced, anti-PD-1-nonresponsive melanoma tumors. We report a harmonized, aggregate resource and suggest that prior CTLA-4 blockade therapy is associated with marked differences in the tumor microenvironment that impact the predictive features of PD-1 blockade therapy response. © 2023 The Authors |
| Keywords: | genetics; metabolism; melanoma; skin neoplasms; tumor marker; skin tumor; immunotherapy; cytotoxic t lymphocyte antigen 4; meta-analysis; tumor microenvironment; immune checkpoint blockade; ctla-4 antigen; humans; human; biomarkers, tumor |
| Journal Title: | Cancer Cell |
| Volume: | 41 |
| Issue: | 4 |
| ISSN: | 1535-6108 |
| Publisher: | Cell Press |
| Date Published: | 2023-04-10 |
| Start Page: | 791 |
| End Page: | 806.e4 |
| Language: | English |
| DOI: | 10.1016/j.ccell.2023.03.010 |
| PUBMED: | 37037616 |
| PROVIDER: | scopus |
| PMCID: | PMC10187051 |
| DOI/URL: | |
| Notes: | The MSK Cancer Center Support Grant (P30 CA008748) is acknowledged in the PubMed record and PDF -- Source: Scopus |
