A step forward in personalized medicine against malignant pleural cancer

Researchers from IDIBELL and ICO establish a new classification of malignant mesothelioma that permits the prediction of the patient’s prognosis and determine those who could benefit from immunotherapy.
The new classification is based on the type of immune cells that infiltrate into tumors.
In parallel, the molecular signature of each group has been determined. This opens the doors to the design of new specific therapies.

In Malignant pleural mesothelioma cancer cells develop in the inner lining of the chest (the pleura). The main cause of this disease is asbestos exposure. It is a very aggressive type of cancer that is difficult to solve with surgery. The routine treatment is usually based on chemotherapy, which, despite improving quality of life, has a modest effect on patient survival. New treatments based on immunotherapy benefit only some patients and, new tools are needed to identify which patients respond better to treatment and which are completely refractory.

A team of researchers from the Oncobell Program of the Bellvitge Biomedical Research Institute (IDIBELL) and the Catalan Institute of Oncology (ICO), led by the Ph.D. candidate Ania Alay, and co-led by Doctors Ernest Nadal and Xavier Solé, has published a study that presents a new classification of malignant mesothelioma. This innovative classification would help to predict the prognosis and response to immunotherapy of patients. This new classification method is based on the quantification of different types of immune cells in tumors using gene expression data from more than 500 tumor samples.

According to these analyzes, the researchers have defined three groups of tumors based on the immune context they presented, groups that are additionally associated with a specific clinical outcome. In addition, they have analyzed the molecular characteristics of each of the groups by analyzing the genomic alterations and the expression profile of different signaling pathways.

The results presented in the Journal for ImmunoTherapy of Cancer show that the group with a shorter life expectancy represents 50% of malignant mesothelioma cases, whereas the group with the best prognosis only represents 8.5% of the cases. However, the molecular signatures that showed the small percentage of patients with a better prognosis indicated that they might have a better response to immunotherapy.

“This new classification can help us to predict the response that the patient will have to therapy, and at the same time allows us to fine-tune the prognosis of each individual. Therefore, doctor, patient, and family could accordingly act this prognosis”, says Dr. Ernest Nadal.

At the same time, Dr. Xavier Solé adds that “the definition of molecular characteristics for each group can be very useful to investigate potential personalized therapies, and highlights the key role of bioinformatics in the precision medicine of the present and the future”.

Ania Alay, for its part, highlights that the basis of this study has been the collection of data from more than 500 publicly available tumors, and that “this study is an example of the importance of making available to all researchers the data collected with molecular techniques. Data theta analyzed carefully can give us a lot of information from different diseases”.

Surveillance of the immune system against cancer

The immune system, which recognizes foreign microorganisms as “not-themselves” and provides a response to destroy these disease-causing agents, plays a similar role in protecting the body against malignancies. Damaged DNA in cancer cells eventually induces the production of abnormal proteins known as tumor antigens. These abnormal tumor proteins mark cancer cells as “not themselves”, and therefore, mark them as targets by the immune system. Still, tumors develop strategies to avoid this attack. That is why the infiltration of immune cells in tumors and their composition are so decisive in the evolution of tumors.

The Bellvitge Biomedical Research Institute (IDIBELL) is a biomedical research center created in 2004. It is participated by the Bellvitge University Hospital and the Viladecans Hospital of the Catalan Health Institute, the Catalan Institute of Oncology, the University of Barcelona and the City Council of L’Hospitalet de Llobregat.

IDIBELL is a member of the Campus of International Excellence of the University of Barcelona HUBc and is part of the CERCA institution of the Generalitat de Catalunya. In 2009 it became one of the first five Spanish research centers accredited as a health research institute by the Carlos III Health Institute. In addition, it is part of the “HR Excellence in Research” program of the European Union and is a member of EATRIS and REGIC. Since 2018, IDIBELL has been an Accredited Center of the AECC Scientific Foundation (FCAECC).