Scientific publications
Conserved Interferon-γ Signaling Drives Clinical Response to Immune Checkpoint Blockade Therapy in Melanoma
Catherine S Grasso 1 , Jennifer Tsoi 2 , Mykola Onyshchenko 2 , Gabriel Abril-Rodriguez 2 , Petra Ross-Macdonald 3 , Megan Wind-Rotolo 3 , Ameya Champhekar 2 , Egmidio Medina 2 , Davis Y Torrejon 2 , Daniel Sanghoon Shin 2 , Phuong Tran 2 , Yeon Joo Kim 2 , Cristina Puig-Saus 4 , Katie Campbell 2 , Agustin Vega-Crespo 2 , Michael Quist 2 , Christophe Martignier 5 , Jason J Luke 6 , Jedd D Wolchok 7 , Douglas B Johnson 8 , Bartosz Chmielowski 2 , F Stephen Hodi 9 , Shailender Bhatia 10 , William Sharfman 11 , Walter J Urba 12 , Craig L Slingluff Jr 13 , Adi Diab 14 , John B A G Haanen 15 , Salvador Martin Algarra 16 , Drew M Pardoll 11 , Valsamo Anagnostou 11 , Suzanne L Topalian 11 , Victor E Velculescu 11 , Daniel E Speiser 5 , Anusha Kalbasi 2 , Antoni Ribas 17
Abstract
We analyze the transcriptome of baseline and on-therapy tumor biopsies from 101 patients with advanced melanoma treated with nivolumab (anti-PD-1) alone or combined with ipilimumab (anti-CTLA-4).
We find that T cell infiltration and interferon-γ (IFN-γ) signaling signatures correspond most highly with clinical response to therapy, with a reciprocal decrease in cell-cycle and WNT signaling pathways in responding biopsies.
We model the interaction in 58 human cell lines, where IFN-γ in vitro exposure leads to a conserved transcriptome response unless cells have IFN-γ receptor alterations. This conserved IFN-γ transcriptome response in melanoma cells serves to amplify the antitumor immune response.
Therefore, the magnitude of the antitumor T cell response and the corresponding downstream IFN-γ signaling are the main drivers of clinical response or resistance to immune checkpoint blockade therapy.
CITA DEL ARTÍCULO Cancer Cell. 2020 Sep 8;S1535-6108(20)30416-5.
doi: 10.1016/j.ccell.2020.08.005
Our authors
