Spatially resolved T cell receptor tracking reveals γδT cell localization to tumor-rich regions in high-risk neuroblastoma: A Report from the Children’s Oncology Group

Jiang Y, Yu W, Wang Y, Thadi A, Pedersen S, Eagles J, Naranjo A, Collins N, DuBois SG, Bagatell R, Crompton BD, Tan K, Pugh TJ. Spatially resolved T cell receptor tracking reveals γδT cell localization to tumor-rich regions in high-risk neuroblastoma: A Report from the Children’s Oncology Group. medRxiv [Preprint]. 2026 Jun 12:2026.06.10.26354144. doi: 10.64898/2026.06.10.26354144. PMID: 42326820; PMCID: PMC13278277.

High-risk neuroblastoma (HRNB) is a leading cause of pediatric cancer death. Current therapies center on intensive multimodal treatment including anti-GD2 therapy, with growing interest in harnessing T cell-mediated immunity. How T cells and their receptors (T-cell receptors, TCRs) are spatially organized and function within tumors remains poorly defined. To assess whether intratumoral location influences clonotype-specific T cell states, we profiled TCR repertoires across blood and tumor samples from 37 patients with HRNB using longitudinal bulk TCR sequencing. In a nested subset of 5 patients with paired pre- and post-therapy tumors, we integrated spatial transcriptomics with in situ TCR profiling. Across all tumors, T and B cells preferentially co-localized in immune-rich regions and showed reduced proximity to neuroblast cells. Despite this compartmentalized architecture, γδT cells were more evenly distributed across tumor sections and showed greater proximity to neuroblast-rich regions than other T cell subsets. Within TCR clonotypes, spatial location was associated with distinct transcriptional states, with immune-rich regions supporting more progenitor-like programs. These findings identify spatial context as a key determinant of phenotype clonotype-specific T cell phenotype and highlight γδT cells cells as a spatially distinct population with potential roles in neuroblastoma tumor-immune interactions.