Las células T intratumorales en tumores cerebrales pediátricos muestran expansión clonal y propiedades efectoras.

Brain tumors in children are a devastating disease in a high proportion of
pacientes. Owing to inconsistent results in clinical trials in unstratified
pacientes, 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.