Abstract IA01: Dumpster-diving into the cancer degradome

Abstract Recently, we uncovered a pivotal role for altered proteasome complex composition in shaping tumor immunogenicity in non-small cell lung cancer (NSCLC). Our research demonstrated that the upregulation of a regulatory cap of the proteasome, PSME4, leads to a reduction in antigenic diversity through alterations in proteasomal cleavage patterns, consequently impeding T-cell-mediated anti-tumor immunity. These findings underscore the importance of probing the tumor degradome and its implications for tumor-immune interactions. Yet, numerous questions remain unanswered: Do specific substrates exhibit preferential degradation in PSME4-capped proteasomes? What constitutes their recognition signal? And fundamentally, how do alterations in the degradation landscape influence tumor inflammation? In my talk, I will delve into our latest advancements in addressing these questions, offering insights into the intricate interplay between proteasome-mediated degradation, tumor inflammation, and STAT signaling. Citation Format: Yifat Merbl. Dumpster-diving into the cancer degradome [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Tumor Immunology and Immunotherapy; 2024 Oct 18-21; Boston, MA. Philadelphia (PA): AACR; Cancer Immunol Res 2024;12(10 Suppl):Abstract nr IA01.