T Cell Response in Pediatric Brain Tumors: Rady Children’s Study Paves the Way for Tailored Immunotherapy Approaches
In a groundbreaking study, Dr. A. Preethi Ganesan, a hematologist and oncologist at Rady Children’s Hospital-San Diego and adjunct assistant professor of pediatrics at UC San Diego School of Medicine, uncovers crucial insights into pediatric brain tumors. This research highlights the role of clonally expanded intra-tumoral T cells with the potential to recognize tumor antigens. Revealing T cell responses and their functional characteristics lays the foundation for more personalized immunotherapy treatments. Dr. Ganesan’s work represents a transformative step towards addressing the complexities of pediatric brain tumor treatment.
Abstract
Brain tumors in children are a devastating disease in a high proportion of patients. Owing to inconsistent results in clinical trials in unstratified patients, the role of immunotherapy remains unclear. We performed an in-depth survey of the single-cell transcriptomes and clonal relationship of intra-tumoral T cells from children with brain tumors. Our results demonstrate that a large fraction of T cells in the tumor tissue are clonally expanded with the potential to recognize tumor antigens. Such clonally expanded T cells display enrichment of transcripts linked to effector function, tissue residency, immune checkpoints, and signatures of neoantigen-specific T cells and immunotherapy response. We identify neoantigens in pediatric brain tumors and show that neoantigen-specific T cell gene signatures are linked to better survival outcomes. Notably, among the patients in our cohort, we observe substantial heterogeneity in the degree of clonal expansion and magnitude of T cell response. Our findings suggest that characterization of intra-tumoral T cell responses may enable selection of patients for immunotherapy, an approach that requires prospective validation in clinical trials.