Your browser doesn't support javascript.
loading
A pan-cancer clinical platform to predict immunotherapy outcomes and prioritize immuno-oncology combinations in early-phase trials.
Hernando-Calvo, Alberto; Vila-Casadesús, Maria; Bareche, Yacine; Gonzalez-Medina, Alberto; Abbas-Aghababazadeh, Farnoosh; Lo Giacco, Deborah; Martin, Agatha; Saavedra, Omar; Brana, Irene; Vieito, Maria; Fasani, Roberta; Stagg, John; Mancuso, Francesco; Haibe-Kains, Benjamin; Han, Ming; Berche, Roger; Pugh, Trevor J; Mirallas, Oriol; Jimenez, Jose; Gonzalez, Nadia Saoudi; Valverde, Claudia; Muñoz-Couselo, Eva; Suarez, Cristina; Diez, Marc; Élez, Elena; Capdevila, Jaume; Oaknin, Ana; Saura, Cristina; Macarulla, Teresa; Galceran, Joan Carles; Felip, Enriqueta; Dienstmann, Rodrigo; Bedard, Philippe L; Nuciforo, Paolo; Seoane, Joan; Tabernero, Josep; Garralda, Elena; Vivancos, Ana.
Affiliation
  • Hernando-Calvo A; Department of Medical Oncology, Vall D'Hebron University Hospital, 08035 Barcelona, Spain; Vall d'Hebron Institute of Oncology, 08035 Barcelona, Spain; Division of Medical Oncology and Hematology, Department of Medicine, Princess Margaret Cancer Centre, University of Toronto, Toronto, ON M5G2C4, Can
  • Vila-Casadesús M; Vall d'Hebron Institute of Oncology, 08035 Barcelona, Spain.
  • Bareche Y; Institut du Cancer de Montréal, Centre de Recherche du Centre Hospitalier de l'Université de Montréal, Montréal, QC H2X0A9, Canada; Faculty of Pharmacy, Université de Montréal, Montréal, QC H3T1J4, Canada.
  • Gonzalez-Medina A; Vall d'Hebron Institute of Oncology, 08035 Barcelona, Spain.
  • Abbas-Aghababazadeh F; Princess Margaret Cancer Centre, University Health Network, Toronto, ON M5G2C4, Canada.
  • Lo Giacco D; Vall d'Hebron Institute of Oncology, 08035 Barcelona, Spain.
  • Martin A; Vall d'Hebron Institute of Oncology, 08035 Barcelona, Spain.
  • Saavedra O; Department of Medical Oncology, Vall D'Hebron University Hospital, 08035 Barcelona, Spain; Vall d'Hebron Institute of Oncology, 08035 Barcelona, Spain.
  • Brana I; Department of Medical Oncology, Vall D'Hebron University Hospital, 08035 Barcelona, Spain; Vall d'Hebron Institute of Oncology, 08035 Barcelona, Spain.
  • Vieito M; Department of Medical Oncology, Vall D'Hebron University Hospital, 08035 Barcelona, Spain; Vall d'Hebron Institute of Oncology, 08035 Barcelona, Spain.
  • Fasani R; Vall d'Hebron Institute of Oncology, 08035 Barcelona, Spain.
  • Stagg J; Institut du Cancer de Montréal, Centre de Recherche du Centre Hospitalier de l'Université de Montréal, Montréal, QC H2X0A9, Canada; Faculty of Pharmacy, Université de Montréal, Montréal, QC H3T1J4, Canada.
  • Mancuso F; Vall d'Hebron Institute of Oncology, 08035 Barcelona, Spain.
  • Haibe-Kains B; Princess Margaret Cancer Centre, University Health Network, Toronto, ON M5G2C4, Canada; Department of Medical Biophysics, University of Toronto, Toronto, ON M5G1L7, Canada; Department of Computer Science, University of Toronto, Toronto, ON M5S2E4, Canada; Ontario Institute for Cancer Research, Toron
  • Han M; Princess Margaret Cancer Centre, University Health Network, Toronto, ON M5G2C4, Canada.
  • Berche R; Vall d'Hebron Institute of Oncology, 08035 Barcelona, Spain.
  • Pugh TJ; Princess Margaret Cancer Centre, University Health Network, Toronto, ON M5G2C4, Canada; Department of Medical Biophysics, University of Toronto, Toronto, ON M5G1L7, Canada; Ontario Institute for Cancer Research, Toronto, ON M5G0A3, Canada.
  • Mirallas O; Department of Medical Oncology, Vall D'Hebron University Hospital, 08035 Barcelona, Spain; Vall d'Hebron Institute of Oncology, 08035 Barcelona, Spain.
  • Jimenez J; Vall d'Hebron Institute of Oncology, 08035 Barcelona, Spain.
  • Gonzalez NS; Department of Medical Oncology, Vall D'Hebron University Hospital, 08035 Barcelona, Spain; Vall d'Hebron Institute of Oncology, 08035 Barcelona, Spain.
  • Valverde C; Department of Medical Oncology, Vall D'Hebron University Hospital, 08035 Barcelona, Spain; Vall d'Hebron Institute of Oncology, 08035 Barcelona, Spain.
  • Muñoz-Couselo E; Department of Medical Oncology, Vall D'Hebron University Hospital, 08035 Barcelona, Spain; Vall d'Hebron Institute of Oncology, 08035 Barcelona, Spain.
  • Suarez C; Department of Medical Oncology, Vall D'Hebron University Hospital, 08035 Barcelona, Spain; Vall d'Hebron Institute of Oncology, 08035 Barcelona, Spain.
  • Diez M; Department of Medical Oncology, Vall D'Hebron University Hospital, 08035 Barcelona, Spain; Vall d'Hebron Institute of Oncology, 08035 Barcelona, Spain.
  • Élez E; Department of Medical Oncology, Vall D'Hebron University Hospital, 08035 Barcelona, Spain; Vall d'Hebron Institute of Oncology, 08035 Barcelona, Spain.
  • Capdevila J; Department of Medical Oncology, Vall D'Hebron University Hospital, 08035 Barcelona, Spain; Vall d'Hebron Institute of Oncology, 08035 Barcelona, Spain.
  • Oaknin A; Department of Medical Oncology, Vall D'Hebron University Hospital, 08035 Barcelona, Spain; Vall d'Hebron Institute of Oncology, 08035 Barcelona, Spain.
  • Saura C; Department of Medical Oncology, Vall D'Hebron University Hospital, 08035 Barcelona, Spain; Vall d'Hebron Institute of Oncology, 08035 Barcelona, Spain.
  • Macarulla T; Department of Medical Oncology, Vall D'Hebron University Hospital, 08035 Barcelona, Spain; Vall d'Hebron Institute of Oncology, 08035 Barcelona, Spain.
  • Galceran JC; Department of Medical Oncology, Vall D'Hebron University Hospital, 08035 Barcelona, Spain; Vall d'Hebron Institute of Oncology, 08035 Barcelona, Spain.
  • Felip E; Department of Medical Oncology, Vall D'Hebron University Hospital, 08035 Barcelona, Spain; Vall d'Hebron Institute of Oncology, 08035 Barcelona, Spain.
  • Dienstmann R; Vall d'Hebron Institute of Oncology, 08035 Barcelona, Spain.
  • Bedard PL; Division of Medical Oncology and Hematology, Department of Medicine, Princess Margaret Cancer Centre, University of Toronto, Toronto, ON M5G2C4, Canada.
  • Nuciforo P; Vall d'Hebron Institute of Oncology, 08035 Barcelona, Spain.
  • Seoane J; Vall d'Hebron Institute of Oncology, 08035 Barcelona, Spain.
  • Tabernero J; Department of Medical Oncology, Vall D'Hebron University Hospital, 08035 Barcelona, Spain; Vall d'Hebron Institute of Oncology, 08035 Barcelona, Spain.
  • Garralda E; Department of Medical Oncology, Vall D'Hebron University Hospital, 08035 Barcelona, Spain; Vall d'Hebron Institute of Oncology, 08035 Barcelona, Spain.
  • Vivancos A; Vall d'Hebron Institute of Oncology, 08035 Barcelona, Spain. Electronic address: avivancos@vhio.net.
Med ; 4(10): 710-727.e5, 2023 10 13.
Article de En | MEDLINE | ID: mdl-37572657
BACKGROUND: Immunotherapy is effective, but current biomarkers for patient selection have proven modest sensitivity. Here, we developed VIGex, an optimized gene signature based on the expression level of 12 genes involved in immune response with RNA sequencing. METHODS: We implemented VIGex using the nCounter platform (Nanostring) on a large clinical cohort encompassing 909 tumor samples across 45 tumor types. VIGex was developed as a continuous variable, with cutoffs selected to detect three main categories (hot, intermediate-cold and cold) based on the different inflammatory status of the tumor microenvironment. FINDINGS: Hot tumors had the highest VIGex scores and exhibited an increased abundance of tumor-infiltrating lymphocytes as compared with the intermediate-cold and cold. VIGex scores varied depending on tumor origin and anatomic site of metastases, with liver metastases showing an immunosuppressive tumor microenvironment. The predictive power of VIGex-Hot was observed in a cohort of 98 refractory solid tumor from patients treated in early-phase immunotherapy trials and its clinical performance was confirmed through an extensive metanalysis across 13 clinically annotated gene expression datasets from 877 patients treated with immunotherapy agents. Last, we generated a pan-cancer biomarker platform that integrates VIGex categories with the expression levels of immunotherapy targets under development in early-phase clinical trials. CONCLUSIONS: Our results support the clinical utility of VIGex as a tool to aid clinicians for patient selection and personalized immunotherapy interventions. FUNDING: BBVA Foundation; 202-2021 Division of Medical Oncology and Hematology Fellowship award; Princess Margaret Cancer Center.
Sujet(s)
Mots clés

Texte intégral: 1 Collection: 01-internacional Base de données: MEDLINE Sujet principal: Tumeurs Type d'étude: Prognostic_studies / Risk_factors_studies Limites: Humans Langue: En Journal: Med Année: 2023 Type de document: Article Pays de publication: États-Unis d'Amérique

Texte intégral: 1 Collection: 01-internacional Base de données: MEDLINE Sujet principal: Tumeurs Type d'étude: Prognostic_studies / Risk_factors_studies Limites: Humans Langue: En Journal: Med Année: 2023 Type de document: Article Pays de publication: États-Unis d'Amérique