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  1. Article ; Online: GS-TCGA: Gene Set-Based Analysis of The Cancer Genome Atlas.

    Baird, Tarrion / Roychoudhuri, Rahul

    Journal of computational biology : a journal of computational molecular cell biology

    2024  Volume 31, Issue 3, Page(s) 229–240

    Abstract: Most tools for analyzing large gene expression datasets, including The Cancer Genome Atlas (TCGA), have focused on analyzing the expression of individual genes or inference of the abundance of specific cell types from whole transcriptome information. ... ...

    Abstract Most tools for analyzing large gene expression datasets, including The Cancer Genome Atlas (TCGA), have focused on analyzing the expression of individual genes or inference of the abundance of specific cell types from whole transcriptome information. While these methods provide useful insights, they can overlook crucial process-based information that may enhance our understanding of cancer biology. In this study, we describe three novel tools incorporated into an online resource; gene set-based analysis of The Cancer Genome Atlas (GS-TCGA). GS-TCGA is designed to enable user-friendly exploration of TCGA data using gene set-based analysis, leveraging gene sets from the Molecular Signatures Database. GS-TCGA includes three unique tools: GS-Surv determines the association between the expression of gene sets and survival in human cancers. Co-correlative gene set enrichment analysis (CC-GSEA) utilizes interpatient heterogeneity in cancer gene expression to infer functions of specific genes based on GSEA of coregulated genes in TCGA. GS-Corr utilizes interpatient heterogeneity in cancer gene expression profiles to identify genes coregulated with the expression of specific gene sets in TCGA. Users are also able to upload custom gene sets for analysis with each tool. These tools empower researchers to perform survival analysis linked to gene set expression, explore the functional implications of gene coexpression, and identify potential gene regulatory mechanisms.
    MeSH term(s) Humans ; Databases, Genetic ; Neoplasms/genetics ; Genome ; Gene Expression Regulation ; Survival Analysis
    Language English
    Publishing date 2024-03-04
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2030900-4
    ISSN 1557-8666 ; 1066-5277
    ISSN (online) 1557-8666
    ISSN 1066-5277
    DOI 10.1089/cmb.2023.0278
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  2. Article ; Online: Orthogonal engineering of synthetic T cell states to enhance cancer immunotherapy.

    Conti, Alberto G / Roychoudhuri, Rahul

    Nature immunology

    2023  Volume 24, Issue 5, Page(s) 733–735

    MeSH term(s) Humans ; Immunotherapy ; T-Lymphocytes ; Neoplasms/genetics ; Neoplasms/therapy ; Immunotherapy, Adoptive ; Genetic Engineering
    Language English
    Publishing date 2023-04-21
    Publishing country United States
    Document type Journal Article ; Comment
    ZDB-ID 2016987-5
    ISSN 1529-2916 ; 1529-2908
    ISSN (online) 1529-2916
    ISSN 1529-2908
    DOI 10.1038/s41590-023-01470-9
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  3. Article ; Online: High-Dimensional Single-Cell Profiling of Tumor-Infiltrating CD4

    Alvisi, Giorgia / Puccio, Simone / Roychoudhuri, Rahul / Scirgolea, Caterina / Lugli, Enrico

    Methods in molecular biology (Clifton, N.J.)

    2022  Volume 2559, Page(s) 243–257

    Abstract: ... ...

    Abstract CD4
    MeSH term(s) Flow Cytometry ; Forkhead Transcription Factors ; Humans ; Immune Tolerance ; Neoplasms ; T-Lymphocytes, Regulatory
    Chemical Substances Forkhead Transcription Factors
    Language English
    Publishing date 2022-09-30
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ISSN 1940-6029
    ISSN (online) 1940-6029
    DOI 10.1007/978-1-0716-2647-4_16
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  4. Article ; Online: Genome-Wide Measurement and Computational Analysis of Transcription Factor Binding and Chromatin Accessibility in Lymphocytes.

    Sadiyah, M Firas / Roychoudhuri, Rahul

    Current protocols in immunology

    2019  Volume 126, Issue 1, Page(s) e84

    Abstract: Cells of the adaptive immune system, including ... ...

    Abstract Cells of the adaptive immune system, including CD4
    MeSH term(s) Animals ; CD4-Positive T-Lymphocytes/physiology ; CD8-Positive T-Lymphocytes/physiology ; Cell Differentiation ; Chromatin/genetics ; Chromatin/metabolism ; Chromatin Assembly and Disassembly ; Computational Biology ; Gene Expression ; Genome ; High-Throughput Nucleotide Sequencing ; Humans ; Lymphocyte Activation ; Organ Specificity ; Protein Binding ; Transcription Factors/metabolism
    Chemical Substances Chromatin ; Transcription Factors
    Language English
    Publishing date 2019-09-02
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2179059-0
    ISSN 1934-368X ; 1934-3671
    ISSN (online) 1934-368X
    ISSN 1934-3671
    DOI 10.1002/cpim.84
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  5. Article: Intracellular K

    Collier, Camille / Wucherer, Kelly / McWhorter, Matthew / Jenkins, Chelsea / Bartlett, Alexandra / Roychoudhuri, Rahul / Eil, Robert

    bioRxiv : the preprint server for biology

    2023  

    Abstract: The cancer-killing activity of T cells is often compromised within tumors, allowing disease progression. We previously found that intratumoral elevations in extracellular K : Synopsis: High extracellular ... ...

    Abstract The cancer-killing activity of T cells is often compromised within tumors, allowing disease progression. We previously found that intratumoral elevations in extracellular K
    Synopsis: High extracellular K
    Language English
    Publishing date 2023-09-15
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2023.09.13.556997
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Intracellular K+ Limits T-cell Exhaustion and Preserves Antitumor Function.

    Collier, Camille / Wucherer, Kelly / McWhorter, Matthew / Jenkins, Chelsea / Bartlett, Alexandra / Roychoudhuri, Rahul / Eil, Robert

    Cancer immunology research

    2023  Volume 12, Issue 1, Page(s) 36–47

    Abstract: T cells are often compromised within cancers, allowing disease progression. We previously found that intratumoral elevations in extracellular K+, related to ongoing cell death, constrained CD8+ T-cell Akt-mTOR signaling and effector function. To ... ...

    Abstract T cells are often compromised within cancers, allowing disease progression. We previously found that intratumoral elevations in extracellular K+, related to ongoing cell death, constrained CD8+ T-cell Akt-mTOR signaling and effector function. To alleviate K+-mediated T-cell dysfunction, we pursued genetic means to lower intracellular K+. CD8+ T cells robustly and dynamically express the Na+/K+ ATPase, among other K+ transporters. CRISPR-Cas9-mediated disruption of the Atp1a1 locus lowered intracellular K+ and elevated the resting membrane potential (i.e., Vm, Ψ). Despite compromised Ca2+ influx, Atp1a1-deficient T cells harbored tonic hyperactivity in multiple signal transduction cascades, along with a phenotype of exhaustion in mouse and human CD8+ T cells. Provision of exogenous K+ restored intracellular levels in Atp1a1-deficient T cells and prevented damaging levels of reactive oxygen species (ROS), and both antioxidant treatment and exogenous K+ prevented Atp1a1-deficient T-cell exhaustion in vitro. T cells lacking Atp1a1 had compromised persistence and antitumor activity in a syngeneic model of orthotopic murine melanoma. Translational application of these findings will require balancing the beneficial aspects of intracellular K+ with the ROS-dependent nature of T-cell effector function. See related Spotlight by Banuelos and Borges da Silva, p. 6.
    MeSH term(s) Humans ; Animals ; Mice ; Reactive Oxygen Species/metabolism ; T-Cell Exhaustion ; Signal Transduction/genetics ; Sodium-Potassium-Exchanging ATPase/genetics ; Sodium-Potassium-Exchanging ATPase/metabolism ; CD8-Positive T-Lymphocytes/metabolism
    Chemical Substances Reactive Oxygen Species ; Sodium-Potassium-Exchanging ATPase (EC 7.2.2.13)
    Language English
    Publishing date 2023-12-08
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2732489-8
    ISSN 2326-6074 ; 2326-6066
    ISSN (online) 2326-6074
    ISSN 2326-6066
    DOI 10.1158/2326-6066.CIR-23-0319
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    Zs.A 7022: Show issues Location:
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  7. Article ; Online: Regulation of regulatory T cells in cancer.

    Stockis, Julie / Roychoudhuri, Rahul / Halim, Timotheus Y F

    Immunology

    2019  Volume 157, Issue 3, Page(s) 219–231

    Abstract: The inflammatory response to transformed cells forms the cornerstone of natural or therapeutically induced protective immunity to cancer. Regulatory T (Treg) cells are known for their critical role in suppressing inflammation, and therefore can ... ...

    Abstract The inflammatory response to transformed cells forms the cornerstone of natural or therapeutically induced protective immunity to cancer. Regulatory T (Treg) cells are known for their critical role in suppressing inflammation, and therefore can antagonize effective anti-cancer immune responses. As such, Treg cells can play detrimental roles in tumour progression and in the response to both conventional and immune-based cancer therapies. Recent advances in our understanding of Treg cells reveal complex niche-specific regulatory programmes and functions, which are likely to extrapolate to cancer. The regulation of Treg cells is reliant on upstream cues from haematopoietic and non-immune cells, which dictates their genetic, epigenetic and downstream functional programmes. In this review we will discuss how Treg cells are themselves regulated in normal and transformed tissues, and the implications of this cross talk on tumour growth.
    MeSH term(s) Animals ; Humans ; Inflammation Mediators/immunology ; Inflammation Mediators/metabolism ; Lymphocytes, Tumor-Infiltrating/immunology ; Lymphocytes, Tumor-Infiltrating/metabolism ; Neoplasms/immunology ; Neoplasms/metabolism ; Neoplasms/pathology ; Phenotype ; Signal Transduction ; T-Lymphocytes, Regulatory/immunology ; T-Lymphocytes, Regulatory/metabolism ; Tumor Escape ; Tumor Microenvironment
    Chemical Substances Inflammation Mediators
    Language English
    Publishing date 2019-05-22
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 80124-0
    ISSN 1365-2567 ; 0019-2805 ; 0953-4954
    ISSN (online) 1365-2567
    ISSN 0019-2805 ; 0953-4954
    DOI 10.1111/imm.13064
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  8. Article ; Online: Regulatory T cells in cancer: where are we now?

    Gallimore, Awen / Quezada, Sergio A / Roychoudhuri, Rahul

    Immunology

    2019  Volume 157, Issue 3, Page(s) 187–189

    Abstract: There have been substantial strides forward in our understanding of the contribution of regulatory T (Treg) cells to cancer immunosuppression. In this issue, we present a series of papers highlighting emerging themes on this topic relevant not only to ... ...

    Abstract There have been substantial strides forward in our understanding of the contribution of regulatory T (Treg) cells to cancer immunosuppression. In this issue, we present a series of papers highlighting emerging themes on this topic relevant not only to our understanding of the fundamental biology of tumour immunosuppression but also to the design of new immunotherapeutic approaches. The substantially shared biology of CD4
    MeSH term(s) Animals ; Humans ; Immunotherapy/adverse effects ; Lymphocytes, Tumor-Infiltrating/immunology ; Lymphocytes, Tumor-Infiltrating/pathology ; Neoplasms/immunology ; Neoplasms/pathology ; Neoplasms/therapy ; Phenotype ; Signal Transduction ; T-Lymphocytes, Regulatory/immunology ; T-Lymphocytes, Regulatory/pathology ; Tumor Escape
    Language English
    Publishing date 2019-06-21
    Publishing country England
    Document type Editorial ; Introductory Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 80124-0
    ISSN 1365-2567 ; 0019-2805 ; 0953-4954
    ISSN (online) 1365-2567
    ISSN 0019-2805 ; 0953-4954
    DOI 10.1111/imm.13088
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  9. Article ; Online: Paths to expansion: Differential requirements of IRF4 in CD8

    Lugli, Enrico / Brummelman, Jolanda / Pilipow, Karolina / Roychoudhuri, Rahul

    European journal of immunology

    2018  Volume 48, Issue 8, Page(s) 1281–1284

    Abstract: Interferon regulatory factor 4 (IRF4) regulates the clonal expansion and metabolic activity of activated T cells, but the precise context and mechanisms of its function in these processes are unclear. In this issue of the European Journal of Immunology, ... ...

    Abstract Interferon regulatory factor 4 (IRF4) regulates the clonal expansion and metabolic activity of activated T cells, but the precise context and mechanisms of its function in these processes are unclear. In this issue of the European Journal of Immunology, Miyakoda et al. [Eur. J. Immunol. 2018. 48: 1319-1328] show that IRF4 is required for activation and expansion of naïve and memory CD8
    MeSH term(s) Animals ; CD8-Positive T-Lymphocytes/immunology ; Cell Differentiation/immunology ; Cell Proliferation ; Immunologic Memory/immunology ; Interferon Regulatory Factors/immunology ; Lymphocyte Activation/immunology ; Mice ; PTEN Phosphohydrolase/metabolism ; Phosphatidylinositol 3-Kinases/metabolism ; Proto-Oncogene Proteins c-akt/metabolism ; Receptors, Antigen, T-Cell/immunology ; Signal Transduction/immunology
    Chemical Substances Interferon Regulatory Factors ; Receptors, Antigen, T-Cell ; interferon regulatory factor-4 ; Phosphatidylinositol 3-Kinases (EC 2.7.1.-) ; Proto-Oncogene Proteins c-akt (EC 2.7.11.1) ; PTEN Phosphohydrolase (EC 3.1.3.67) ; Pten protein, mouse (EC 3.1.3.67)
    Language English
    Publishing date 2018-08-22
    Publishing country Germany
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 120108-6
    ISSN 1521-4141 ; 0014-2980
    ISSN (online) 1521-4141
    ISSN 0014-2980
    DOI 10.1002/eji.201847727
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  10. Article ; Online: Epigenetic control of CD8

    Henning, Amanda N / Roychoudhuri, Rahul / Restifo, Nicholas P

    Nature reviews. Immunology

    2018  Volume 18, Issue 5, Page(s) 340–356

    Abstract: Upon stimulation, small numbers of naive ... ...

    Abstract Upon stimulation, small numbers of naive CD8
    MeSH term(s) Animals ; CD8-Positive T-Lymphocytes/cytology ; CD8-Positive T-Lymphocytes/immunology ; CD8-Positive T-Lymphocytes/metabolism ; Cell Differentiation/genetics ; Cell Differentiation/immunology ; Cellular Reprogramming Techniques/methods ; Chromatin Assembly and Disassembly/genetics ; Chromatin Assembly and Disassembly/immunology ; DNA Methylation/immunology ; Enhancer Elements, Genetic ; Epigenesis, Genetic/immunology ; Histone Code/genetics ; Humans ; Immunotherapy/methods ; Models, Genetic ; Models, Immunological ; Transcription, Genetic
    Language English
    Publishing date 2018-01-30
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 2062776-2
    ISSN 1474-1741 ; 1474-1733
    ISSN (online) 1474-1741
    ISSN 1474-1733
    DOI 10.1038/nri.2017.146
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