NEW YORK – Research from the department of Immunology & Inflammation in the pharmaceutical company Regeneron was published recently in the prestigious scientific journal Nature Cancer and uncovered the different identities that the cells of the immune system acquire in the fight against cancer.
During cancer initiation and progression, cancer cells continuously interact with the cells of the immune system of the patient. Although in the initial disease stages the immune system keeps cancer under control, once the efficacy of the immune system declines, disease progresses. The molecular mechanisms that transform effective immune cells into dysfunctional ones are poorly understood.
The investigator Dr. Nikos Kourtis and colleagues, under the leadership of Dr. Dimitris Skokos, Senior Director of the department of Cancer Immunology at Regeneron, mapped the molecular identities of immune cells in renal cancer. By analyzing patient samples at the single-cell level, they profiled immune cells derived from tumor at multiple levels. The scientists discovered extensive heterogeneity in the molecular identities of T lymphocytes, a critical immune cell population in the battle against cancer. “We understand for the first time and with unprecedented resolution, the various states of immune cells in patients with renal cancer and why the immune system stops working efficiently,” said Dr. Kourtis.
Remarkably, the scientists found that a molecular pathway that up until now was known for its beneficial role in the biology of T cells acquires a new function in cancer and leads to death of T cells. Also, the investigators discovered molecular signatures that can predict the life expectancy of the patients with renal cancer. “Our study opens the road for precision medicine and selection of patients for personalized therapies based on the molecular identities of the patient’s immune cells,” said Dr. Skokos.
As part of this study, researchers identified novel potential mechanisms that drive dysfunction of T cells during cancer progression. According to Kourtis and Skokos these results may help the design of novel drugs aiming at immune system reinvigoration in the fight against cancer.
More information is available online: https://www.regeneron.com.
The article in Nature Cancer is also available online: https://go.nature.com/3IlROoF.
The Greek scientists spoke with The National Herald about their research.
When asked about their background, where in Greece they grew up and studied, Dr. Kourtis said, “I grew up in Athens and graduated from the department of Biology of the National and Kapodistrian University of Athens. Next, I obtained my PhD from the Institute of Molecular Biology and Biotechnology (IMBB) and the University of Crete. Then, I moved to the U.S. to continue my training as a postdoctoral fellow at New York University (NYU). In 2019, I joined Regeneron where I do research on cancer immunology in Dimitris’ ‘Cancer Immunology’ team.”
Dr. Skokos told TNH: “I was born in Athens, Greece. I received my PhD and master’s degrees in molecular immunology from the Pasteur Institute, University Paris 5, Rene Descartes School of Medicine, and my BSc in cellular immunology and physiology from University Paris, France. Prior to joining Regeneron, I was a post-doctoral fellow at the Rockefeller University, working with Ralph Steinman (Nobel Laureate 2011) and Michel Nussenzweig. I joined Regeneron in 2008 as Staff Scientist and now I serve as Senior Director of Cancer Immunology. My team is responsible for developing the next generation of combination immunotherapeutic strategies including the costimulatory bispecific antibodies and other foundational antibody medicines to treat cancer.”
When asked if they were always interested in pursuing a career in science, Kourtis said, “I was always curious about the cause behind the observation. Science keeps us excited 24/7 and I cannot imagine myself doing anything different. I am the first person in my family who went to university, but for my parents my education was always the absolute priority, so I owe everything to them.”
Skokos said: “The reason for choosing a career in science and medical research was my curiosity of human disease development, and the desire to find a cure with the hope of potentially saving patients’ lives.”
When asked about this specific research project, they told TNH: “We started working on this project just before the beginning of the pandemic. Despite the challenges we encountered along the way, the talent, the motivation and commitment of Regeneron’s scientists enabled us to generate an important and meaningful dataset. We are very happy to share our findings with the rest of the scientific community.”
Of the real-world implications of their research, they said: “The advancement and availability of single -cell technologies, enables us to investigate with unprecedented resolution how immune cells fight cancer. In our study, we found that not all immune cells are equally effective in attacking cancer. By better understanding which patients may require a boost of their immune response, we may be able to design appropriate drugs to support the fight against cancer.”