The Immune Regulation Laboratory, co-funded by IIGM and the Armenise-Harvard Foundation, addresses fundamental aspects of the immune responses, related to memory T cell differentiation and long-term protection.
In the last years, numerous innovations in cancer treatment demonstrate that long-lasting clinical benefits can be obtained by targeting CD8+ T lymphocyte responses. These observations have determined a paradigm shift in cancer treatment: to target the immune cells to improve tumor rejection.
Following Ag recognition, activated CD8+ T lymphocytes expand and differentiate into short-lived effector and long-lived memory subsets. The main research focus of the laboratory aims to understand how T lymphocytes integrate complex environmental stimuli and translate these signals into specific epigenetic and differentiation programs, which specify T cell fate commitment and function. We analyze the impact of heterochromatin factors on the establishment and maintenance of memory CD8+ T cell stemness, plasticity and effector differentiation in the context of cancer.
The research's goal is to use this knowledge to develop novel strategies for the prevention and treatment of cancer, in the new and promising field of cancer immunotherapy.
Innovative aspects: the research program is based on a multidisciplinary study, by looking at interchangeable and reversible epigenetic factors as major drivers of T cell fate determination. We combine a variety of approaches, including relevant immunological models of infectious diseases and cancer, translational models, advanced imaging, genetic and genomic techniques, including high throughput cell-based assays, next generation sequencing (NGS) of RNA and epigenetic marks.
Added value: This work will provide new insights in our fundamental understanding of T cell functional identity and fate commitment. This study will reveal new fundamental properties of T lymphocytes and new molecular and epigenetic targets, thus opening to novel perspectives in CD8+ T cell manipulation in cancer immunotherapy and vaccine development.
1. Pace L., Goudot C., Zueva E., Quivy JP., G. Almouzni & S. Amigorena. Epigenetic control of "stemness" in CD8+ T cell memory development. Full article. SCIENCE 2018; 359(6372): 177-186. Highlighted in a Perspective in the same issue.
2. Alloatti A., Kotsias F., Pauwels AM., Carpier JM., Jouve M, Timmerman E., #Pace L., Vargas P., Maurin M., Gehrmann U., Joannas L., Vivar OI., Lennon-Duménil AM., Savina A., Gevaert Beyaert R., Hoffmann E., Amigorena S. Toll-like Receptor 4 Engagement on Dendritic Cells Restrains Phago-Lysosome Fusion and Promotes Cross-Presentation of Antigens. IMMUNITY. 43(6):1087-100, 2015.
3. Pace L., Tempez A., Arnold-Schrauf C., Lemaitre F., Bousso P., Fetler L;, Sparwasser T., Amigorena S. Regulatory T cells increase the avidity of primary CD8+ T cell responses and promote memory. SCIENCE. 2012; 338 (6106): 532-6. 18 stars Faculty 1000, and highlighted in Nature Immunological Review 2012.
• Luigia Pace, Principal investigator (IIGM)
• Giusy Granato Post-doc (IIGM)
• Valentina Russo fellow (IIGM)
• Nadia Brasu master 2 student (UniTo, IIGM)
• Luca Petitti, Post-doc (IIGM)
• Gaia Montacchiesi, intern (UniTo)
• Role of heterochromatin in T lymphocyte memory development.