Treatment of cancer has been revolutionized by immune checkpoint blockade therapies. Despite the high rate of response in advanced melanoma, the majority of patients succumb to disease. To identify factors associated with success or failure of checkpoint therapy, we profiled transcriptomes of 16,291 individual immune cells from 48 tumor samples of melanoma patients treated with checkpoint inhibitors. Two distinct states of CD8+ T cells were defined by clustering and associated with patient tumor regression or progression. A single transcription factor, TCF7, was visualized within CD8+ T cells in fixed tumor samples and predicted positive clinical outcome in an independent cohort of checkpoint-treated patients. We delineated the epigenetic landscape and clonality of these T cell states and demonstrated enhanced antitumor immunity by targeting novel combinations of factors in exhausted cells. Our study of immune cell transcriptomes from tumors demonstrates a strategy for identifying predictors, mechanisms, and targets for enhancing checkpoint immunotherapy.
Pubmed ID: 30388456 RIS Download
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View all literature mentionsJava toolset for working with next generation sequencing data in the BAM format.
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View all literature mentionsMulti paradigm numerical computing environment and fourth generation programming language developed by MathWorks. Allows matrix manipulations, plotting of functions and data, implementation of algorithms, creation of user interfaces, and interfacing with programs written in other languages, including C, C++, Java, Fortran and Python. Used to explore and visualize ideas and collaborate across disciplines including signal and image processing, communications, control systems, and computational finance.
View all literature mentionsSoftware performing alignment of high-throughput RNA-seq data. Aligns RNA-seq reads to reference genome using uncompressed suffix arrays.
View all literature mentionsSoftware ultrafast memory efficient tool for aligning sequencing reads. Bowtie is short read aligner.
View all literature mentionsSoftware package for quantifying gene and isoform abundances from single end or paired end RNA Seq data. Accurate transcript quantification from RNA Seq data with or without reference genome. Used for accurate quantification of gene and isoform expression from RNA-Seq data.
View all literature mentionsOriginal SAMTOOLS package has been split into three separate repositories including Samtools, BCFtools and HTSlib. Samtools for manipulating next generation sequencing data used for reading, writing, editing, indexing,viewing nucleotide alignments in SAM,BAM,CRAM format. BCFtools used for reading, writing BCF2,VCF, gVCF files and calling, filtering, summarising SNP and short indel sequence variants. HTSlib used for reading, writing high throughput sequencing data.
View all literature mentionsA tool for annotating human genomic point mutations and indels with data relevant to cancer researchers. Genomic Annotations, Protein Annotations, and Cancer Annotations are aggregated from many resources. A standalone version of Oncotator is being developed.
View all literature mentionsA software tool (and method) for estimating the amount of cross-sample contamination in next generation sequencing data.
View all literature mentionsSoftware tools for Motif Discovery and next-gen sequencing analysis. Used for analyzing ChIP-Seq, GRO-Seq, RNA-Seq, DNase-Seq, Hi-C and numerous other types of functional genomics sequencing data sets. Collection of command line programs for unix style operating systems written in Perl and C++.
View all literature mentionsSoftware for the reliable and accurate identification of somatic point mutations in next generation sequencing data of cancer genomes.
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.
View all literature mentionsStatistical analysis software that combines scientific graphing, comprehensive curve fitting (nonlinear regression), understandable statistics, and data organization. Designed for biological research applications in pharmacology, physiology, and other biological fields for data analysis, hypothesis testing, and modeling.
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.
View all literature mentionsSoftware tool to enable biologists without training in computer vision or programming to quantitatively measure phenotypes from thousands of images automatically. It counts cells and also measures the size, shape, intensity and texture of every cell (and every labeled subcellular compartment) in every image. It was designed for high throughput screening but can perform automated image analysis for images from time-lapse movies and low-throughput experiments. CellProfiler has an increasing number of algorithms to identify and measure properties of neuronal cell types.
View all literature mentionsThis monoclonal targets CD3epsilon
View all literature mentionsMus musculus with name BALB/cJ from IMSR.
View all literature mentionsThis monoclonal targets CD28
View all literature mentionsThis monoclonal targets CD3
View all literature mentionsThis monoclonal targets TNF-?
View all literature mentionsThis monoclonal targets IL-2
View all literature mentionsThis monoclonal targets IFN-?
View all literature mentionsThis recombinant monoclonal targets Granzyme B
View all literature mentionsThis monoclonal targets Perforin
View all literature mentionsThis monoclonal targets IFN-gamma
View all literature mentionsThis monoclonal targets IL-2
View all literature mentionsThis monoclonal targets TNF-alpha
View all literature mentionsThis monoclonal targets CD90.2
View all literature mentionsThis monoclonal targets CD90.2
View all literature mentionsThis monoclonal targets CD45.2
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 CD8a
View all literature mentionsThis monoclonal targets CD3epsilon
View all literature mentionsThis monoclonal targets CD3epsilon
View all literature mentionsMus musculus with name C57BL/6J from IMSR.
View all literature mentionsThis monoclonal targets CD366
View all literature mentionsThis monoclonal targets CD39
View all literature mentionsThis monoclonal targets CD8a
View all literature mentionsThis monoclonal targets CD4
View all literature mentionsThis monoclonal targets CD39
View all literature mentionsThis monoclonal targets HLA-A
View all literature mentionsThis monoclonal targets CD3
View all literature mentionsThis monoclonal targets CD45
View all literature mentionsThis monoclonal targets CD16/32
View all literature mentionsThis monoclonal targets CD8α
View all literature mentionsThis monoclonal targets IFNγ
View all literature mentionsThis monoclonal targets PD-1 (CD279)
View all literature mentionsThis isotype control targets KLH
View all literature mentionsThis monoclonal targets CD8α
View all literature mentionsThis monoclonal targets CTLA-4 (CD152)
View all literature mentionsThis monoclonal targets PD-1 (CD279)
View all literature mentionsThis monoclonal targets TIM-3 (CD366)
View all literature mentionsThis isotype control targets Trinitrophenol
View all literature mentionsThis monoclonal targets CD279
View all literature mentionsThis monoclonal targets CD3
View all literature mentionsThis monoclonal targets CD235a
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View all literature mentionsThis monoclonal targets CD8a
View all literature mentionsThis monoclonal targets CD28
View all literature mentionsMus musculus with name BALB/cJ from IMSR.
View all literature mentions