Research
Autoimmunity and Tolerance
Autoimmunity is a consequence of the breakdown of self-tolerance leading the immune system to attack organs and tissues. Autoimmune diseases have no cure until now and comprise a wide spectrum of diseases that collectively affect approximately 5 to 10% of the developed world population and are a significant cause of morbidity and mortality. The pathogenesis of autoimmune diseases involves a particular combination of genetic, immune, hormonal, and environmental factors. Although to this date some factors such as sunlight exposure affecting vitamin D levels, nutritional habits, xenobiotics, and hygiene have been associated to autoimmunity, the true cause of the breaking of the immune balance is still largely unknown.
We work on trying to understand the mechanisms involved in the development of autoimmune diseases. We believe that an altered traffic and localization of antigen presenting cells such as dendritic cells and B-lymphocytes are key components in the development of these diseases.
Immune System and Cancer
Our research focuses on the intricate role of the immune system in combating cancer, particularly the function and challenges of cytotoxic CD8+ T cells in tumor eradication. Despite the presence of these cells, cancer often progresses due to an immunosuppressive tumor microenvironment rich in adenosine, leading to T cell exhaustion. A critical finding is that a subset of these exhausted cells, known as TPEX (precursors of exhausted T cells), characterized by TCF1 expression, responds effectively to PD1 therapy. These TPEX cells possess stem-like properties, enabling them to persist and self-renew, serving as a reservoir within tumors.
Our research investigates the dual role of adenosine in the tumor microenvironment. While adenosine is known for its immunosuppressive effects, promoting T cell exhaustion via A2A receptors, it also appears to support CD8+ T cell stemness and survival. This duality suggests that complete blockade of adenosine signaling could reduce TPEX cell frequency and impact the effectiveness of PD1 therapy. Our hypothesis posits that adenosine, produced by CD73, promotes the differentiation of CD8+ T cells into TPEX cells, influencing the therapeutic response to immune checkpoint blockade.
Resident Memory B cells