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Checkpoint blockade mediates a proliferative response of tumor-infiltrating CD8+ T lymphocytes (TILs). The origin of this response has remained elusive because chronic activation promotes terminal differentiation or exhaustion of tumor-specific T cells. Here we identified a subset of tumor-reactive TILs bearing hallmarks of exhausted cells and central memory cells, including expression of the checkpoint protein PD-1 and the transcription factor Tcf1. Tcf1+PD-1+ TILs mediated the proliferative response to immunotherapy, generating both Tcf1+PD-1+ and differentiated Tcf1-PD-1+ cells. Ablation of Tcf1+PD-1+ TILs restricted responses to immunotherapy. Tcf1 was not required for the generation of Tcf1+PD-1+ TILs but was essential for the stem-like functions of these cells. Human TCF1+PD-1+ cells were detected among tumor-reactive CD8+ T cells in the blood of melanoma patients and among TILs of primary melanomas. Thus, immune checkpoint blockade relies not on reversal of T cell exhaustion programs, but on the proliferation of a stem-like TIL subset.
Pubmed ID: 30635237 RIS Download
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Software repository for R packages related to analysis and comprehension of high throughput genomic data. Uses separate set of commands for installation of packages. Software project based on R programming language that provides tools for analysis and comprehension of high throughput genomic data.
View all literature mentionsSoftware for single-cell flow cytometry analysis. Its functions include management, display, manipulation, analysis and publication of the data stream produced by flow and mass cytometers.
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View all literature mentionsRegistry and results database of federally and privately supported clinical trials conducted in United States and around world. Provides information about purpose of trial, who may participate, locations, and phone numbers for more details. This information should be used in conjunction with advice from health care professionals.Offers information for locating federally and privately supported clinical trials for wide range of diseases and conditions. Research study in human volunteers to answer specific health questions. Interventional trials determine whether experimental treatments or new ways of using known therapies are safe and effective under controlled environments. Observational trials address health issues in large groups of people or populations in natural settings. ClinicalTrials.gov contains trials sponsored by National Institutes of Health, other federal agencies, and private industry. Studies listed in database are conducted in all 50 States and in 178 countries.
View all literature mentionsSoftware performing alignment of high-throughput RNA-seq data. Aligns RNA-seq reads to reference genome using uncompressed suffix arrays.
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View all literature mentionsThis unknown targets Armenian Hamster IgG (H+L)
View all literature mentionsThis polyclonal targets IgG (H+L)
View all literature mentionsThis polyclonal secondary targets IgG (H+L)
View all literature mentionsThis polyclonal secondary targets IgG (H+L)
View all literature mentionsThis unknown targets Rat IgG (H+L)
View all literature mentionsThis polyclonal secondary targets IgG (H+L)
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View all literature mentionsThis polyclonal secondary targets IgG (H+L)
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View all literature mentionsThis monoclonal targets PD-1 (CD279)
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View all literature mentionsThis monoclonal targets CD223 (LAG-3)
View all literature mentionsThis monoclonal targets IL-2
View all literature mentionsThis monoclonal targets KLRG1
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View all literature mentionsThis monoclonal targets CD185 (CXCR5)
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View all literature mentionsThis monoclonal targets CD45.2
View all literature mentionsThis monoclonal targets CD4
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View all literature mentionsThis monoclonal targets CD3e
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View all literature mentionsAllele Detail: Targeted This is a legacy resource.
View all literature mentionsThe genome of the domesticated dog, a close evolutionary relation to human, is a powerful new tool for understanding the human genome. Comparison of the dog with human and other mammals reveals key information about the structure and evolution of genes and genomes. The unique breeding history of dogs, with their extraordinary behavioral and physical diversity, offers the opportunity to find important genes underlying diseases shared between dogs and humans, such as cancer, diabetes, and epilepsy. The Canine Genome Sequencing Project produced a high-quality draft sequence of a female boxer named Tasha. By comparing Tasha with many other breeds, the project also compiled a comprehensive set of SNPs (single nucleotide polymorphisms) useful in all dog breeds. These closely spaced genomic landmarks are critical for disease mapping. By comparing the dog, rodent, and human lineages, researchers at the Broad Institute uncovered exciting new information about human genes, their evolution, and the regulatory mechanisms governing their expression. Using SNPs, researchers describe the strikingly different haplotype structure in dog breeds compared with the entire dog population. In addition, they show that by understanding the patterns of variation in dog breeds, scientists can design powerful gene mapping experiments for complex diseases that are difficult to map in human populations. Contribute Although the astounding generosity of Eli and Edythe L. Broad and several other venture philanthropists empowers our scientists to tackle many of the most important problems at the cutting edge of genomic medicine, there are many other critical challenges that they cannot yet pursue because of limited resources. We need additional visionary partners to join the Broads and the Broad Institute in transforming medicine with the power of genomics.
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View all literature mentionsBioconductor software package for Empirical analysis of Digital Gene Expression data in R. Used for differential expression analysis of RNA-seq and digital gene expression data with biological replication.
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View all literature mentionsScript distributed with the HT-Seq Python framework for processing RNA-seq or DNA-seq data.
View all literature mentionsSoftware performing alignment of high-throughput RNA-seq data. Aligns RNA-seq reads to reference genome using uncompressed suffix arrays.
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View all literature mentionsMus musculus with name C57BL/6-Tg(TcraTcrb)1100Mjb/J from IMSR.
View all literature mentionsAllele Detail: Transgenic This is a legacy resource.
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laboratory mouse with name B6.SJL-PtprcaPepc
Cell line E.G7-OVA is a Cancer cell line with a species of origin Mus musculus (Mouse)
View all literature mentionsCell line B16-F10 is a Cancer cell line with a species of origin Mus musculus (Mouse)
View all literature mentionsCell line YUMM1.7 is a Cancer cell line with a species of origin Mus musculus (Mouse)
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