For a long time, our immune defenses had remained in the background of the fight against cancer. However, in recent years, Inserm Research Director Jérôme Galon has endeavored to show that they actually play a major role. Efforts which have earned him the European Inventor Award 2019 for his test, Immunoscore®. Applied in the clinical setting, it uses the immune system response of cancer patients to predict their risk of relapse and as such adjust their treatment.
A pioneering researcher in cancer immunology, Galon has amassed prestigious publications and awards for his work. But the latest, the European Inventor Award 2019, acknowledges another aspect of his professional life: his talent as entrepreneur. "I had always wanted to create a company to showcase my team’s discoveries. It is an honor that Immunoscore® has been selected from among the 165,000 patents filed each year in Europe", declares the immunologist, delighted. This success is also the confirmation that our immune system well and truly has its place in the fight against cancer.
Galon acquired his passion for immunology from Professor Michel Seman when doing his Masters in 1992 at Jussieu. "I was fascinated by the concept of self/non-self and by the immune system’s great capacity to adapt. It is incredible how our defenses recognize everything!", he enthuses. Following his post-graduate diploma (DEA) at Institut Pasteur and PhD at Institut Curie,
which he defended in 1996, Galon headed across the Atlantic to Bethesda – a few miles north of Washington and home to the US National Institutes of Health (NIH), the world’s largest biomedical research agency. "I have excellent memories of this postdoc. It was amazing – the resources were limitless! We used the most cutting-edge techniques, anything was possible. And being in close proximity to the greatest specialists created such an energy. It was a revelation and I knew then that research was something I wanted to continue doing", he remembers.
Whilst still in the USA, Galon applied for and obtained in 2000 an Inserm position at Cordeliers Research Center* in Paris. Back at Jussieu, he endeavored to develop a research project in a field that the majority of oncologists and clinicians did not find worthy of interest at the time: cancer immunology.
A complete paradigm shift
"I was convinced that the expertise in genome sequencing and gene expression analysis I acquired in the US could be useful in this discipline." The young group leader then set about contacting clinicians to obtain access to patient cohorts, developing IT infrastructures to host databases and studying the tumor environment of cancerous tissues. "It was a long and difficult undertaking", he recalls. But in 2005 the initial results came in.
"When analyzing the immune parameters of over 900 colon cancer patients, we were surprised to note that the spread of metastases was blocked in some of them by memory T cells." Thanks to the action of these white blood cells whose role is to recognize a threat faced by our immune system in the past, the relapse risk was lower in these patients. A finding which could bring about changes to the entire cancer classification system used to determine prognosis and treatment. Tumors are classified according to their location, characteristics, such as their aggressiveness, and the presence of metastases. "However, T cells play an essential role in tumor progression. By determining their presence in the tumor, their type, their number and the quality of their immune response, we have been able to more precisely predict relapse risk in patients with colon cancer. It is a complete paradigm shift", declares Galon. A concept which was then given the name "immune contexture" following the 2006 publication of these findings in the prestigious journal Science.
Predicting patient relapse risk
It was at that point that a certain entrepreneurial spirit kicked in, with Galon deciding that this research had to have a clinical impact. His objective? Develop a test to predict the relapse risk of patients in order to offer them the most suitable treatment. He began by filing numerous patents with the help of Inserm Transfert and then co-founded a startup, HalioDx, in 2014. A company which at present employs over 170 people, including some twenty in the USA, and distributes Immunoscore® in 28 countries. Concretely, this test characterizes this immune contexture in tumor tissue, which is analyzed using a specialized scanner and its T cell content determined using an algorithm. The higher the number of these immune cells, the higher the Immunoscore® and the greater the chances of survival. Validated firstly in colon cancer, this prognostic tool is also available for use in non-small cell lung cancer (NSCLC) – with other types of cancer expected to follow. What is more, patients with a high Immunoscore® respond better to chemotherapy and potentially also to immunotherapy, treatments which boost immune defenses against tumors. Ultimately, Immunoscore® could therefore also be used to predict patient response to treatment. "It is important for me to see that not only do these discoveries have a public health impact, they have also enabled me to create a dynamic company", he smiles.
And it is notably on the basis of these two criteria that the European Patent Office awarded Galon the European Inventor Award 2019 in the category Research. "Scientifically I could not ask for anything more, and none of these discoveries would have been possible without the support of Inserm and the help of my colleagues, such as Franck Pagès from Hôpital Européen Georges Pompidou in Paris." And he does not intend to stop there. His team’s latest research, published in Nature, suggests that the immune system could detect changes in cells even before cancer develops Which could pave the way for treatments that stimulate our immune defenses before the tumors form. The future of immunology in oncology is therefore looking very bright indeed.
1992. Master of Immunology, Institut Pasteur, Paris
1992-1996. PhD in Immunology, Institut Curie, Paris
1997-2001. Postdoctoral fellowship at NIH, Bethesda, USA
2001. Group Leader, Inserm
Since 2007. Research Director at Inserm and Integrative Cancer Immunology Team Leader at Cordeliers Research Center, Paris
* unit 1138 Inserm/ Université Paris Diderot/Université Paris Descartes/Sorbonne Université, Cordeliers Research Center, Integrative Cancer Immunology team, Paris