Humanitas immunologist receives 1.25 million dollar grant from the Cancer Research Institute to study the immune system of cancer patients

A 1.25 million dollar, five-year grant aimed at studying immune responses in cancer patients. In July, an important economic recognition arrived from the Cancer Research Institute (CRI)   a private non-profit American foundation based in New York, which, for the first time, supports an Italian project. The winning project is the one carried out by Dr. Enrico Lugli, head of the Laboratory of Translational Immunology and of the Flow Cytometry Core at Fondazione Humanitas per la Ricerca. “The recognition from the CRI is of great pride for us, also because the project was selected by a committee of world-famous scientists who have pioneered the development of novel immunotherapeutic approaches for the treatment of cancer” says Dr. Lugli. “This is of utmost importance for me, because it gives support to research that is considered a hope for the future. I would not have been able to achieve such a goal without the expertise and passion of my research team”.

The team coordinated by Lugli is formed by twelve scientists, including PhD students, post-docs, bioinformaticians, a medical oncologist and technicians specialized in advanced technologies. For years the Laboratory of Translational Immunology at the Fondazione Humanitas per la Ricerca has been involved in “studying the immune system in the context of cancer and since 2011 we have witnessed a revolution, since the approval of the so-called immunotherapeutic drugs capable of reawakening the patient’s own immune system against the tumour”. These are drugs that can “remove the brakes of the immune response, especially at the level of the T cells (a specialized population of immune cells) which can then mediate tumor destruction.” The problem lies, as Lugli explains, “in the fact that only part of the treated patients has a durable response to the treatments. The most significant discovery we have made concerns the type of cells involved in the immune response. Notoriously, T cells are present in tumours but are considered dysfunctional in their entirety. Instead, we found that they respond to a hierarchy, according to which a small population, later termed stem-like cells, maintains the ability to exert a powerful immune response in the long term.” On this topic, the team coordinated by Lugli has made several publications resulting from the work in the laboratory. “Unlike a few years ago, we now know more precisely the target of these immunotherapies, thereby allowing us to develop more targeted approaches to enhance immune function.”

These results are also fundamental to immunotherapy approaches for blood cancers that are based on so-called cell transfer, whereby the patient’s circulating immune cells are isolated, modified in the laboratory to make them capable of attacking the cancer cells, and then reinfused. However, clinical protocols still have limitations because immune responses can be of limited duration or develop resistance. “In this area,” Lugli clarifies, “we and other research groups have found that transferring stem-like T cells works very well for these types of cancers, so what we’re trying to figure out now is how to increase the potency of the stem-like T cells by reprogramming their behaviour in the lab before infusion.

The hope is to identify the molecular mechanisms that underlie durable immune responses, so that those patients who are now resistant can be made sensitive to current immunotherapies.” For all of this, the financial support that has come from the CRI is of central importance.