Celeste Nicola

As a PhD student at Université de Rouen Normandie, I became particularly interested in how tumoral immune microenvironment shapes systemic immunity beyond tumor control. Using tumor-bearing mouse models, I investigated the effects of immune checkpoint inhibitors (antiPD-1/PD-L1), demonstrating that, while effective against cancer, they alter systemic immune responses in ways that promote neuroinflammation and lead to measurable impairments in brain functions. This work highlighted the systemic consequences of tumor immunity and motivated me to further explore how immune-tumor interactions can affect the nervous system in clinical contexts. I then pursued a one-year postdoctoral fellowship at the national reference center for paraneoplastic neurological syndromes (PNS) in Lyon. PNS are rare disorders caused by an immune cross-reaction, where tumors aberrantly express neuronal antigens and trigger anti-tumor responses that also attack the nervous system. The origin of this immune attack remains poorly understood. Drawing on my expertise in tumor biology, I contributed to a complementary line of research aimed at investigating the tumors themselves as potential initiators of tolerance breakdown. Thanks to unique access to rare patient tumor samples, I characterized their biological features and identified alterations such as increased lymphangiogenesis, which may facilitate antigen drainage and enhance presentation of neuronal antigens. Building on this experience, for my upcoming postdoc at Yale University, I will focus on the brain to complete the picture of cancer-associated neurological disease. Specifically, I will apply immunopeptidomic approaches to map the neuronal antigenic landscape, in order to understand how immune recognition of neural targets contributes to pathology.