Intra-tumoral T cells in pediatric brain tumors display clonal expansion and effector properties.

in Nature cancer by Aditi Upadhye, Kevin E Meza Landeros, Ciro Ramírez-Suástegui, Benjamin J Schmiedel, Edwin Woo, Serena J Chee, Denise Malicki, Nicole G Coufal, David Gonda, Michael L Levy, Jason A Greenbaum, Grégory Seumois, John Crawford, William D Roberts, Stephen P Schoenberger, Hilde Cheroutre, Christian H Ottensmeier, Pandurangan Vijayanand, Anusha-Preethi Ganesan

TLDR

  • The study analyzed single-cell transcriptomes and clonal relationships of intra-tumoral T cells from children with brain tumors and found that clonally expanded T cells display enrichment of transcripts linked to effector function and neoantigen-specific T cells.
  • The study identified neoantigens in pediatric brain tumors and showed that neoantigen-specific T cell gene signatures are linked to better survival outcomes.
  • The study's findings may enable selection of patients for immunotherapy and improve treatment outcomes for children with brain tumors.

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.

Overview

  • The study aims to investigate the role of immunotherapy in treating brain tumors in children by analyzing the single-cell transcriptomes and clonal relationships of intra-tumoral T cells.
  • The study surveyed 50 children with brain tumors and found that a large fraction of T cells in the tumor tissue are clonally expanded and have the potential to recognize tumor antigens.
  • The study aimed to determine whether characterizing intra-tumoral T cell responses can enable selection of patients for immunotherapy, which requires prospective validation in clinical trials.

Comparative Analysis & Findings

  • The study found that 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.
  • The study identified neoantigens in pediatric brain tumors and showed that neoantigen-specific T cell gene signatures are linked to better survival outcomes.
  • The study observed substantial heterogeneity in the degree of clonal expansion and magnitude of T cell response among patients.

Implications and Future Directions

  • The study's findings suggest that characterization of intra-tumoral T cell responses may enable selection of patients for immunotherapy, which has the potential to improve treatment outcomes for children with brain tumors.
  • The study's results may help inform the development of personalized immunotherapy approaches for pediatric brain tumors.
  • Future studies should focus on validating the results of this study in larger cohorts and exploring the potential of neoantigen-specific T cells as a biomarker for immunotherapy response.
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