153 Spatial Transcriptomic Profiling of T Cell Exhaustion Markers in Atypical Teratoid Rhabdoid Tumor Subtypes

INTRODUCTION: Atypical teratoid/rhabdoid tumor (ATRT) is one of the most common brain tumors in pediatric populations. Despite advances in treatment, overall survival remains poor and novel effective therapies are needed. METHODS: Tumor purities of 49 atypical ATRT tumors, encompassing 3 epigenetic subtypes (MYC, SHH, TYR) were estimated using known mRNA expression signatures of stromal and immune cells. Using the purity estimates and bulk tumor expression values, non-negative linear regression was implemented to estimate the average expression of each gene in the stromal and tumor compartments for each subtype. RESULTS: Compared to other subtypes, SHH-ATRTs expressed relatively higher levels of T-cell immunoglobulin domain and mucin domain protein 3 (TIM-3) and its ligand GAL9. MYC-ATRTs expressed higher levels of numerous T cell inhibitory receptors including lymphocyte activation gene 3 protein (LAG-3), band T lymphocyte attenuator (BTLA), cytotoxic T lymphocyte antigen-4 (CTLA-4), and programmed cell death protein 1 (PD-1). CONCLUSIONS: The predicted stromal and tumor compartment deconvolution yielded previously unrecognized expression patterns of T cell exhaustion markers which should be evaluated further to develop effective targeted therapies for ATRT.