Publicaciones científicas

Conserved Interferon-γ Signaling Drives Clinical Response to Immune Checkpoint Blockade Therapy in Melanoma

08-sep-2020 | Revista: Cancer Cell

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

Nuestros autores