Immunotherapy empowers the immune system to fight cancer by helping it recognize and attack tumor cells. While this therapeutic strategy continues to revolutionize the treatment of an increasing number of tumor types, it fails to achieve clinical responses in many patients and does not yield benefit in the treatment of many cancers. There is, therefore, an unmet clinical need to identify predictive biomarkers of response for selecting those patients who would most likely benefit from immune-based therapies.
Published in the Cell Press’ Med, the results of a study led by researchers of The Vall d’Hebron Institute of Oncology (VHIO)’s Cancer Genomics Group led by Ana Vivancos, PhD, and Research Unit for Molecular Therapy of Cancer (UITM) – CaixaResearch directed by Elena Garralda, MD, have preliminarily validated the VHIO gene expression signature (VIGex) as a tool for classifying solid tumors based on the expression level of genes involved in the adaptive immune response, and a predictor of patients' response to immunotherapy.
“To address this limitation, we developed a pan-cancer platform to measure the activation of genes implicated in the antitumor immune response. We analyzed the gene expression of more than 1000 samples from VHIO’s institutional molecular prescreening program, our Advanced Molecular Diagnostics Program supported by the FERO Foundation,” explains Vivancos, corresponding author of this study.
What is VIGex?
VIGex—developed in-house as a predictive platform to help guide patient selection for immunotherapy—is an optimized gene signature based on the expression level of 12 key genes implicated in the activation of the immune response. This novel tool has been designed to classify solid tumors into three categories based on the inflammatory status of the tumor microenvironment: “hot”, “intermediate-cold,” and “cold”. PD-1/PD-L1 checkpoint inhibitors (ICIs) have been shown to work best against hot tumors, while they generally fail to yield benefit in the treatment of cold tumors.
The predictive power of VIGex was initially observed in a cohort of 98 refractory solid tumors from patients treated in early-phase immunotherapy clinical trials performed at VHIO’s UITM–CaixaResearch. The investigators subsequently validated the test in a metanalysis with more than 800 tumor samples from previously published studies with clinical and gene expression datasets available to the scientific community.
In the initial validation cohort treated with immunotherapy agents under development in early-phase clinical trials, the authors observed better responses in those patients with tumors classified as hot. “In addition to measuring the inflammatory status of the tumor microenvironment, we generated a pan-cancer biomarker platform that integrated VIGex categories with the gene expression levels of immunotherapy targets in early-phase drug development,” adds Vivancos.
How will VIGex be used in clinical research?
“The development of this tool will improve the selection of patients who are more likely to benefit from immuno-oncology across tumor types and different immune-based treatments. As part of this international collaboration, our VIGex signature will be applied to data from an immunotherapy clinical trial conducted at the Princess Margaret Cancer Centre in Toronto,” said Garralda, who is also a co-author of this study.
VIGex will also be used as a biomarker in a prospective clinical trial of the European Organisation for Research and Treatment of Cancer (EORTC), funded by the Spanish Association Against Cancer (AECC), for head and neck cancer patients treated with immunotherapy. “Our results support the clinical utility of VIGex as a tool to aid oncologists in patient selection for trials testing personalized immunotherapy. In the future, this could lead to the expansion of VIGex as a predictive marker for novel immuno-oncology combinations in early-phase clinical studies,” concludes Ana Vivancos.
- This press release was originally published on the Vall d'Hebron Institute of Oncology website