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Updated: Jul 19, 2025
Immunophenotyping of Orthotopic Homograft Syngeneic of Murine Primary KPC Pancreatic Ductal Adenocarcinoma by Flow Cytometry
Published on: October 9, 2018
A pan-cancer clinical platform to predict immunotherapy outcomes and prioritize immuno-oncology combinations in
Alberto Hernando-Calvo1, Maria Vila-Casadesús2, Yacine Bareche3
1Department 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, Canada; Departamento de Medicina, Universidad Autónoma de Barcelona (UAB), 08035 Barcelona, Spain.
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.
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