Comprehensive immunological profiling of NUT carcinoma in children, adolescents and young adults by ultra-high content imaging - Search for immunological targets in an especially unfavorable subgroup of patients

Abstract

This dissertation explores potential therapeutic targets for NUT carcinoma (NC), a rare and aggressive cancer with few treatment options, by examining its tumor microenvironment (TME) through immunohistochemistry, and advanced multiplex imaging, using the MACSima system. A customized immuno-oncology antibody panel is established and applied to analyze the TME of NCs in detail and explore potential therapeutic targets. The study additionally compares long-term and short-term survivors (cut-off value 6 months) to identify prognostic markers. Key findings of this study reveal that NCs exhibited significantly greater immune infiltration than previously anticipated, challenging the prior understanding that NCs are "cold tumors" with limited immune involvement. These results provide important new insights into TME of NCs, a subject with little prior knowledge. Immune profiling of the TME show notable differences between survivor groups, with short-term survivors exhibiting higher levels of granulocytes, M2 macrophages, and exhausted T-cells, as well as an increased intratumoral lymphocyte-togranulocyte ratio. With few established prognostic factors especially regarding the TME, the prognostic factors identified in this study, including immune cell profiles and their relation to survival outcomes, can help pinpoint high-risk patients, enabling more effective therapeutic stratification and personalized treatment approaches for patients with NC. Additionally, this study reveals that the examined NCs predominantly expressed CD276 and EGFR, identifying these molecules as promising targets for therapeutic intervention that could potentially prolong survival through targeted immunotherapy.

Die Dissertation ist gesperrt bis zum 31. Dezember 2027 !