Abstract LB-065: A high quality neoantigen fitness model cooperates with T lymphocyte infiltrates to identify glioblastoma patients with the longest survival

Malignant glioma (glioblastoma, GBM) is a lethal cancer resistant to multimodality therapeutic approaches. A high burden of tumor-specific mutant peptides (neoantigens) correlates with a more favorable prognosis and response to immunotherapies in selected solid tumors but the role of neoantigens and how they impact clinical outcome in most tumors including GBM remains unclear. Here, we exploited the similarity between tumor neoantigens and infectious disease-derived immune epitopes and applied a neoantigen fitness model for the identification of high quality neoantigens in human GBM. The neoantigen quality fitness model stratified GBM patients with more favorable clinical outcome and, together with tumor infiltration of CD8 T lymphocytes, identified a subgroup of GBM patients with the longest survival, thus exhibiting optimal performance. Conversely, neither tumor neoantigen burden from a quantity model nor the isolated enrichment of CD8 T lymphocytes could predict better survival of GBM patients. The GBM subgroup that emerged from the neoantigen quality model displays distinct genomic and transcriptomic features that should guide patient stratification for immunotherapy and maximal benefit of GBM patients. Citation Format: Jing Zhang, Francesca P. Caruso, Jason K. Sa, Sune Justesen, Do-Hyun Nam, Peter Sims, Michele Ceccarelli, Anna Lasorella, Antonio Iavarone. A high quality neoantigen fitness model cooperates with T lymphocyte infiltrates to identify glioblastoma patients with the longest survival [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr LB-065.