Upadhye and Meza Landeros et al. used scRNAseq and TCRseq on pediatric brain tumor samples, and found that a large fraction of intratumoral T cells were clonally expanded and specific for tumor antigens. These clonally expanded T cells were enriched for transcripts linked to effector functions, tissue residency, immune checkpoints, and signatures associated with neoantigen-specific T cells and immunotherapy responses. Specific neoantigens were identified, along with neoantigen-specific T cell signatures that were associated with longer survival, though samples showed substantial heterogeneity in T cell clonal expansion and response.
Contributed by Lauren Hitchings
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.
Author Info: (1) La Jolla Institute for Immunology, La Jolla, CA, USA. (2) La Jolla Institute for Immunology, La Jolla, CA, USA. Center for Genomic Sciences, National Autonomous University of M
Author Info: (1) La Jolla Institute for Immunology, La Jolla, CA, USA. (2) La Jolla Institute for Immunology, La Jolla, CA, USA. Center for Genomic Sciences, National Autonomous University of Mexico, Cuernavaca, Mexico. (3) La Jolla Institute for Immunology, La Jolla, CA, USA. (4) La Jolla Institute for Immunology, La Jolla, CA, USA. (5) Southampton University Hospitals NHS Trust, Southampton, UK. (6) Department of Respiratory Medicine, Liverpool Heart and Chest Hospital NHS Foundation Trust, Liverpool, UK. Department of Molecular and Clinical Cancer Medicine, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool, UK. (7) Department of Pathology, University of California San Diego, La Jolla, CA, USA. Rady Children's Hospital, San Diego, CA, USA. (8) Rady Children's Hospital, San Diego, CA, USA. Department of Pediatrics, University of California San Diego, La Jolla, CA, USA. (9) Rady Children's Hospital, San Diego, CA, USA. Department of Neurological Surgery, University of California San Diego, La Jolla, CA, USA. (10) Rady Children's Hospital, San Diego, CA, USA. Department of Neurological Surgery, University of California San Diego, La Jolla, CA, USA. (11) La Jolla Institute for Immunology, La Jolla, CA, USA. (12) La Jolla Institute for Immunology, La Jolla, CA, USA. (13) Rady Children's Hospital, San Diego, CA, USA. Department of Neurosciences, University of California San Diego, La Jolla, CA, USA. Department of Pediatrics, University of California Irvine, Irvine, CA, USA. Children's Hospital Orange County, Irvine, CA, USA. (14) Rady Children's Hospital, San Diego, CA, USA. Department of Pediatrics, University of California San Diego, La Jolla, CA, USA. (15) La Jolla Institute for Immunology, La Jolla, CA, USA. (16) La Jolla Institute for Immunology, La Jolla, CA, USA. (17) La Jolla Institute for Immunology, La Jolla, CA, USA. Department of Molecular and Clinical Cancer Medicine, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool, UK. Clatterbridge Cancer Center NHS Foundation Trust, Liverpool, UK. (18) La Jolla Institute for Immunology, La Jolla, CA, USA. vijay@lji.org. Department of Molecular and Clinical Cancer Medicine, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool, UK. vijay@lji.org. Department of Medicine, University of California San Diego, La Jolla, CA, USA. vijay@lji.org. (19) La Jolla Institute for Immunology, La Jolla, CA, USA. preethi@lji.org. Rady Children's Hospital, San Diego, CA, USA. preethi@lji.org. Department of Pediatrics, University of California San Diego, La Jolla, CA, USA. preethi@lji.org.
