Haanen, J. (J.)
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- Conserved interferon-g signaling drives clinical response to immune checkpoint blockade therapy in melanoma(Elsevier, 2020) Vega-Crespo, A. (Agustin); Kalbasi, A. (Anusha); Onyshchenko, M. (Mykola); Grasso, C.S. (Catherine S.); Speiser, D.E. (Daniel E.); Wind-Rotolo, M. (Megan); Ribas, A. (Antoni); Ross-Macdonald, P. (Petra); Diab, A. (Adi); Martin-Algarra, S. (Salvador); Sanghoon-Shin, D. (Daniel); Urba, W.J. (Walter J.); Campbell, K. (Katie); Champhekar, A. (Ameya); Medina, E. (Egmidio); Hodi, F.S. (F. Stephen); Johnson, D.B. (Douglas B.); Anagnostou, V. (Valsamo); Luke, J.J. (Jason J.); Tsoi, J. (Jennifer); Haanen, J. (J.); Tran, P. (Phuong); Velculescu, V.E. (Victor E.); Bhatia, S. (Shailender); Wolchok, J.D. (Jedd D.); Abril-Rodriguez, G. (Gabriel); Topalian, S.L. (Suzanne L.); Chmielowski, B. (Bartosz); Puig-Saus, C. (Cristina); Torrejon, D.Y. (Davis Y.); Joo-Kim, Y. (Yeon); Quist, M. (Michael); Martignier, C. (Christophe); Sharfman, W. (William); Slingluff, C.L. (Craig L.); Pardoll, D.M. (Drew M.)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.
- Starting the fight in the tumor: expert recommendations for the development of human intratumoral immunotherapy (HIT-IT)(Elsevier, 2018) Tersago, D. (Dominique); Massacesi, C. (C.); Klumper, E. (E.); Robert, C. (C.); Rahimian, S. (S.); Kumar, R. (R.); Hendriks, M. (M.); Tabernero, J. (J.); Douillard, J.Y. (J. Y.); Andtbacka, R. (R.); Leidner, R. (R.); Baurain, J.F. (J. F.); Haanen, J. (J.); Marabelle, A. (Aurelien); Stern, M. (M.); Harrington, K. (K.); Brody, J. (J.); Baere, T. (T.) de; Melero, I. (Ignacio); Tse, A. (A.); Imperiale, M. (M.); Tchakov, I. (I.); Ascierto, P.A. (Paolo Antonio); Öhrling, K. (K.)A European Society for Medical Oncology (ESMO)-sponsored expert meeting was held in Paris on 8 March 2018 which comprised 11 experts from academia, 11 experts from the pharmaceutical industry and 2 clinicians who were representatives of ESMO. The focus of the meeting was exclusively on the intratumoral injection/delivery of immunostimulatory agents with the aim of harmonizing the standard terms and methodologies used in the reporting of human intratumoral immunotherapy (HIT-IT) clinical trials to ensure quality assurance and avoid a blurring of the data reported from different studies. The goal was to provide a reference document, endorsed by the panel members that could provide guidance to clinical investigators, pharmaceutical companies, ethics committees, independent review boards, patient advocates and the regulatory authorities and promote an increase in the number and quality of HIT-IT clinical trials in the future. Particular emphasis was placed not only on the development of precise definitions to facilitate a better understanding between investigators but also on the importance of systematic serial biopsies as a driver for translational research and the need for the recording and reporting of data, to facilitate a better understanding of the key processes involved.