Over recent years, tumors with a higher density of infiltrating immune cells, termed as ‘hot’ tumors, have been shown to be more responsive to treatment with immune checkpoint inhibitors (ICIs) than non-inflamed, ‘cold’ tumors. Aimed at better predicting response to these immune-based therapies in cancer patients, VHIO’s Cancer Genomics Group directed by Dr. Ana Vivancos has developed a gene-expression signature, VIGex, to classify patients’ samples into Hot, intermediate-Cold, and Cold subgroups by measuring the level of gene activation involved in IFN-g mediated immune response.
The predictive power of VIGex in detecting those patients who are most likely to obtain clinical benefit from immunotherapy was initially validated in patients treated with ICIs in phase I immuno-oncology clinical trials performed at VHIO’s Research Unit for Molecular Therapy of Cancer (UITM) – CaixaResearch(1), directed by Dr. Elena Garralda, at the Vall d’Hebron University Hospital – HUVH (Vall d’Hebron Barcelona Hospital Campus).
Now, results of collaborative research carried out by VHIO researchers and investigators at the Princess Margaret Cancer Centre, University Health Network in Toronto, (ON, Canada), were selected by the American Society of Clinical Oncology (ASCO) to first outing as an oral presentation during a Clinical Science Symposium(2) at this week’s 2022 ASCO Annual Meeting, 03 – 07 June 2022, Chicago (IL, USA).
Presented by first author Alberto Hernando-Calvo, formerly a phase I investigator at our UITM-CaixaResearch who is now a Medical Oncology Fellow at the Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre,latest data further validate VIGex as a novel predictive biomarker for immune checkpoint treatment in patients with advanced solid tumors.
“Data from this collaborative research show that VIGex maintained its predictive power of outcomes from therapy with ICIs when applied to an independent external dataset using RNA-sequencing. VIGex combined with circulating tumor DNA analysis by liquid biopsy can refine the identification of responders to cancer immunotherapy,” says Dr. Ana Vivancos, Principal Investigator of VHIO’s Cancer Genomics Group and co-author of this study alongside Elena Garralda, Director of the UITM-CaixaResearch.
Using data from 76 patients with advanced solid tumors receiving treatment with pembrolizumab in the in the phase II INSPIRE study led by Lillian Siu at the Princess Margaret Cancer Centre, University Health Network, the investigators performed ctDNA analyses at treatment initiation and at the start of cycle 3. Based on the VIGex-generated results, two main subgroups were defined: HOT, with greater tumor inflammation, and COLD, with little or no inflammation.
“By combining these data with the results of our liquid biopsy analyses, we were able to establish that patients who responded best to therapy with this ICI were those with inflamed, so-called hot tumors. These tumors showed reduced levels of ctDNA after the start of treatment,” adds Dr. Alberto Hernando-Calvo, first author of this present study.
“Changes in ctDNA levels further improved the performance of VIGex in predicting overall patient survival. These findings could help generate new hypotheses on combinations of predictive biomarkers for cancer immunotherapy toward the more precise selection of patients who could benefit from these treatments,” concludes Dr. Alberto Hernando-Calvo, whose research at the Princess Margaret Cancer Centre is supported by a Fellowship Grant from the Spanish Society of Medical Oncology (SEOM), and the CRIS Cancer Foundation.
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