Project 2: Deciphering the Dynamic Evolution of the Tumor-Immune Interface

This application is being submitted in response to the Notice of Special Interest (NOSI) identified as NOT-CA24-029.

Glioblastoma (GBM) is a lethal form of brain cancer with a median overall survival of 15 months and a 5-year survival rate of less than 5%.

In situ vaccination strategies combining immunogenic chemotherapy and innate immune adjuvants have been proposed to overcome immunotherapy resistance due to their ability to potently control tumor growth while providing tumor antigens and co-stimulatory adjuvants to activate anti-tumor immune responses and generate immune memory.

However, despite the promise of these combinations and their immunomodulatory activity across numerous cell types, no studies have examined how these therapies impact the antigen repertoires presented by tumor and antigen-presenting cells (APCs) and how changes in antigen repertoires affect survival and therapeutic mechanisms.