Abstract 1198: T cell receptor (TCR) landscape of childhood brain tumors

Abstract T lymphocytes have a unique ability to recognize a vast array of antigens prompt by an enormous T cell receptor (TCR) repertoire. Characterization of tumor-infiltrating T cells (TILs) is key to understand MHC-restricted anti-tumor immunity and for developing T cell-centered immunotherapies such as adoptive cell therapy and tumor vaccines. In the current work, we investigated RNA-Seq data from 997 pediatric brain tumor patients and performed a large-scale comprehensive examination of the immunogenomic and TCR landscape of TILs across the entire spectrum of pediatric brain tumors. We show that the relative ratio between T cell clonal diversity and T cell abundance within each sample, represented by the clonal expansion index (CEI), is a strong predictor of prognosis both within and between tumor types. Interestingly, we show that CEI is strongly associated with molecular subgroups of medulloblastoma but not with known genomic features of these subgroups. Investigation of TCR clonotypes recognizing a common recurrent tumor-antigen across patients based on CDR3 homology and characteristics, reveals 9 TCR clusters which are tumor-type restricted with defined prognoses and HLA dominance. Using computational immunogenomics and machine learning-based investigations of these clusters we identified novel putative HLA-restricted tumor antigens which could bind and activate the clusters’ specific TCRs. Importantly, our framework grounded the foundations for developing a precision medicine approach of T cell-centered immunotherapies. These findings have major implications for understanding the interplay between T cell and tumor genomics, and for developing new immunotherapies for children with brain tumors and other cancers. Citation Format: Itay Raphael, Michal Nisnboym, Rebecca A. Raphael, Shikhar Uttam, Ian F. Pollack, Maria Chikina, Dhivyaa Rajasundaram, Gary Kohanbash. T cell receptor (TCR) landscape of childhood brain tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1198.