Identify patients with liver cancer who respond best to immunotherapy. To make it possible is a study, partly Italian, which has identified for the first time a molecular signature of liver cancer that predicts sensitivity to these drugs. An important discovery if we consider that, also thanks to it, the European Society for Organ Transplantation (ESOT) has decided to include immunotherapy for liver tumors as a neo-adjuvant treatment (which is performed before surgery) in the its next guidelines: a change that could allow transplantation in some cases currently excluded from this possibility.
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A molecular signature to predict the efficacy of immunotherapy
In the study, published in Gastroenterologyresearchers – including Vincent Mazzaferro, Director of the Complex Structure of Hepato-Gastro-Pancreatic Surgery of the National Cancer Institute of Milan (INT) and professor of surgery at the University of Milan (UniMi) – have identified a sort of “molecular label” capable of determining increase the probability of success of immunotherapy drugs. “We identified a predictive molecular signature, called IFNAP, which is made up of the combination of eleven genes,” explains Mazzaferro: “This signature predicts the sensitivity of liver cancer tumor cells to the anti-PD1 class of immunotherapy drugs, regardless of the origin of the tumor itself”.
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To identify the presence of the IFNAP molecular signature on the tumor, the scientists tested two methods: a prognostic biopsy performed directly on the tumor tissue and a liquid biopsy, which can identify and extract tumor cell fragments in the blood. The latter, as shown by a second study published in Gut, has been shown to be able to correctly identify treatable patients in 90% of cases. With an undoubted advantage also for the patient who only undergoes a blood sample.
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Immunotherapy in liver cancer
In recent years, immunotherapy drugs have been playing an increasingly important role in the treatment of tumors previously considered incurable. It is a therapy that enhances the action of the immune system by recruiting a large number of cells capable of recognizing and destroying cancer cells. The problem, in the case of liver cancer, is that only 20% of treated patients respond positively, and so far research has not been able to identify which factors depend on the outcome. That’s why identifying a molecular signature that predicts the efficacy of immunotherapy is so important.
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Enhance the effectiveness of immunotherapy drugs
In addition to identifying in which cases immunotherapy can work to fight liver cancer, researchers are also studying strategies to increase its effectiveness, as demonstrated by further research published in Gut. “Physical treatments such as radio-embolization can prepare the ground for the actual therapy – continues Mazzaferro -. In practice, they stimulate the production of specific tumor antigens, capable of activating groups of immunocompetent cells against the tumor, which will then be enhanced by immunotherapeutic drugs”.
ESOT decision
These studies not only broaden the range of therapeutic solutions for the treatment of liver cancer – currently the fifth most frequent cause of death from cancer worldwide – but can change the strategic approach to the treatment of this type of tumour. “It will still take further research to obtain increasingly personalized therapies,” he concludes Sherrie Bhoori, specialist in gastroenterology and hepatology of the INT – but the decision of the European Society for Organ Transplantation is significant: having examined the results of the scientific works, the inclusion of neo-adjuvant immunotherapy in the next European Guidelines was approved. This therapeutic approach therefore becomes one of the possible strategies to be adopted in selected cases, particularly when the molecular signature is present”.