How metabolism bridles cytotoxic CD8+ T cells through epigenetic modifications

Mitochondrial stress induced by continuous stimulation under hypoxia rapidly drives T cell exhaustion

(2021) Nicole E. Scharping et al.   NATURE IMMUNOLOGY

Low-dose decitabine priming endows CAR T cells with enhanced and persistent antitumour potential via epigenetic reprogramming

(2021) Yao Wang et al.   Nature Communications

Methionine Metabolism Shapes T Helper Cell Responses through Regulation of Epigenetic Reprogramming

(2020) Dominic G. Roy et al.   Cell Metabolism

The phosphatase PAC1 acts as a T cell suppressor and attenuates host antitumor immunity

(2020) Dan Lu et al.   NATURE IMMUNOLOGY

Developmental plasticity allows outside-in immune responses by resident memory T cells

(2020) Raissa Fonseca et al.   NATURE IMMUNOLOGY

Decitabine Augments Chemotherapy-Induced PD-L1 Upregulation for PD-L1 Blockade in Colorectal Cancer

(2020) Kevin Chih-Yang Huang et al.   Cancers

Developmental Relationships of Four Exhausted CD8+ T Cell Subsets Reveals Underlying Transcriptional and Epigenetic Landscape Control Mechanisms

(2020) Jean-Christophe Beltra et al.   IMMUNITY

Divergent Effects of Dnmt3a and Tet2 Mutations on Hematopoietic Progenitor Cell Fitness

(2020) Elizabeth L. Ostrander et al.   Stem Cell Reports

Metabolic signaling in T cells

(2020) Justin A. Shyer et al.   CELL RESEARCH

DNA methyltransferases in hematological malignancies

(2020) Nguyet M. Hoang et al.   Journal of Genetics and Genomics

Impaired mitochondrial oxidative phosphorylation limits the self-renewal of T cells exposed to persistent antigen

(2020) Santosha A. Vardhana et al.   NATURE IMMUNOLOGY

The histone methyltransferase DOT1L prevents antigen-independent differentiation and safeguards epigenetic identity of CD8+ T cells

(2020) Eliza Mari Kwesi-Maliepaard et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Rewriting History: Epigenetic Reprogramming of CD8+ T Cell Differentiation to Enhance Immunotherapy

(2020) Caitlin C. Zebley et al.   TRENDS IN IMMUNOLOGY

Targeting Nuclear LSD1 to Reprogram Cancer Cells and Reinvigorate Exhausted T Cells via a Novel LSD1-EOMES Switch

(2020) Wen Juan Tu et al.   Frontiers in Immunology

An open-label, phase II multicohort study of an oral hypomethylating agent CC-486 and durvalumab in advanced solid tumors

(2020) Kirsty Taylor et al.   Journal for ImmunoTherapy of Cancer

RORα Regulates Cholesterol Metabolism of CD8+ T Cells for Anticancer Immunity

(2020) In Kyu Lee et al.   Cancers

Epigenetic Control of Cdkn2a.Arf Protects Tumor-Infiltrating Lymphocytes from Metabolic Exhaustion

(2020) Brian Koss et al.   CANCER RESEARCH

Cancer SLC43A2 alters T cell methionine metabolism and histone methylation

(2020) Yingjie Bian et al.   NATURE

Coordinative metabolism of glutamine carbon and nitrogen in proliferating cancer cells under hypoxia

(2019) Yuanyuan Wang et al.   Nature Communications

Mitochondrial superoxide disrupts the metabolic and epigenetic landscape of CD4+ and CD8+ T-lymphocytes

(2019) C.M. Moshfegh et al.   Redox Biology

IL-15-mediated reduction of mTORC1 activity preserves the stem cell memory phenotype of CAR-T cells and confers superior antitumor activity

(2019) Darya Alizadeh et al.   Cancer Immunology Research

Molecular and Genetic Characterization of MHC Deficiency Identifies EZH2 as Therapeutic Target for Enhancing Immune Recognition

(2019) Daisuke Ennishi et al.   Cancer Discovery

T cell stemness and dysfunction in tumors are triggered by a common mechanism

(2019) Suman Kumar Vodnala et al.   SCIENCE

Hypoxia induces rapid changes to histone methylation and reprograms chromatin

(2019) Michael Batie et al.   SCIENCE

Histone demethylase KDM6A directly senses oxygen to control chromatin and cell fate

(2019) Abhishek A. Chakraborty et al.   SCIENCE

Targeting epigenetic modifications in cancer therapy: erasing the roadmap to cancer

(2019) Helai P. Mohammad et al.   NATURE MEDICINE

Subsets of exhausted CD8+ T cells differentially mediate tumor control and respond to checkpoint blockade

(2019) Brian C. Miller et al.   NATURE IMMUNOLOGY

NR4A transcription factors limit CAR T cell function in solid tumours

(2019) Joyce Chen et al.   NATURE

Sequentially inducible mouse models reveal that Npm1 mutation causes malignant transformation of Dnmt3a-mutant clonal hematopoiesis

(2019) Matthew A. Loberg et al.   LEUKEMIA

Optimization of 4-1BB antibody for cancer immunotherapy by balancing agonistic strength with FcγR affinity

(2019) Xinyue Qi et al.   Nature Communications

Acetate Promotes T Cell Effector Function during Glucose Restriction

(2019) Jing Qiu et al.   Cell Reports

Antigen receptor control of methionine metabolism in T cells

(2019) Linda V Sinclair et al.   eLife

TOX is a critical regulator of tumour-specific T cell differentiation

(2019) Andrew C. Scott et al.   NATURE

Dietary methionine influences therapy in mouse cancer models and alters human metabolism

(2019) Xia Gao et al.   NATURE

Advances in epigenetics link genetics to the environment and disease

(2019) Giacomo Cavalli et al.   NATURE

TOX transcriptionally and epigenetically programs CD8+ T cell exhaustion

(2019) Omar Khan et al.   NATURE

Single-cell RNA-seq reveals TOX as a key regulator of CD8+ T cell persistence in chronic infection

(2019) Chen Yao et al.   NATURE IMMUNOLOGY

TOX and TOX2 transcription factors cooperate with NR4A transcription factors to impose CD8+ T cell exhaustion

(2019) Hyungseok Seo et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

miR-155 harnesses Phf19 to potentiate cancer immunotherapy through epigenetic reprogramming of CD8+ T cell fate

(2019) Yun Ji et al.   Nature Communications

Selective HDAC6 inhibitors improve anti-PD-1 immune checkpoint blockade therapy by decreasing the anti-inflammatory phenotype of macrophages and down-regulation of immunosuppressive proteins in tumor cells

(2019) Tessa Knox et al.   Scientific Reports

Degradation of D-2-hydroxyglutarate in the presence of isocitrate dehydrogenase mutations

(2019) Raffaela S. Berger et al.   Scientific Reports

Targeting Adenosine in Cancer Immunotherapy to Enhance T-Cell Function

(2019) Selena Vigano et al.   Frontiers in Immunology

Chimeric Antigen Receptor-Modified T Cell Therapy in Multiple Myeloma: Beyond B Cell Maturation Antigen

(2019) Marijke Timmers et al.   Frontiers in Immunology

An Evolutionarily Conserved Function of Polycomb Silences the MHC Class I Antigen Presentation Pathway and Enables Immune Evasion in Cancer

(2019) Marian L. Burr et al.   CANCER CELL

Anti-CAR-engineered T cells for epitope-based elimination of autologous CAR T cells

(2019) Stefanie Koristka et al.   CANCER IMMUNOLOGY IMMUNOTHERAPY

Targeting EZH2 enhances antigen presentation, antitumor immunity and circumvents anti-PD-1 resistance in head and neck cancers

(2019) Liye Zhou et al.   CLINICAL CANCER RESEARCH

Impaired T cell proliferation by ex vivo BET-inhibition impedes adoptive immunotherapy in a murine melanoma model

(2019) Jonathan Chee et al.   Epigenetics

The Transcription Factor Bhlhe40 Programs Mitochondrial Regulation of Resident CD8+ T Cell Fitness and Functionality

(2019) Chaofan Li et al.   IMMUNITY

A novel germline variant in the DOT1L gene co-segregating in a Dutch family with a history of melanoma

(2019) Catarina Salgado et al.   MELANOMA RESEARCH

The emerging role of epigenetic therapeutics in immuno-oncology

(2019) Michael J. Topper et al.   Nature Reviews Clinical Oncology

Immunity, Hypoxia and Metabolism - the ménage à trois of cancer: implications for immunotherapy

(2019) Carla Riera-Domingo et al.   PHYSIOLOGICAL REVIEWS

Non-catalytic Roles of Tet2 Are Essential to Regulate Hematopoietic Stem and Progenitor Cell Homeostasis

(2019) Kyoko Ito et al.   Cell Reports

Reactive Oxygen Species in the Tumor Microenvironment: An Overview

(2019) Frank Weinberg et al.   Cancers

A cellular antidote to specifically deplete anti-CD19 chimeric antigen receptor positive cells

(2019) Marco Ruella et al.   BLOOD

Metabolic Profiling Using Stable Isotope Tracing Reveals Distinct Patterns of Glucose Utilization by Physiologically Activated CD8+ T Cells

(2019) Eric H. Ma et al.   IMMUNITY

Metabolic regulation of gene expression by histone lactylation

(2019) Di Zhang et al.   NATURE

Glutamine blockade induces divergent metabolic programs to overcome tumor immune evasion

(2019) Robert D. Leone et al.   SCIENCE

Modulation of SRSF2 expression reverses the exhaustion of TILs via the epigenetic regulation of immune checkpoint molecules

(2019) Ziqiang Wang et al.   CELLULAR AND MOLECULAR LIFE SCIENCES

Tumor-Repopulating Cells Induce PD-1 Expression in CD8 + T Cells by Transferring Kynurenine and AhR Activation

(2018) Yuying Liu et al.   CANCER CELL

Autophagy and T cell metabolism

(2018) Samuel D. Dowling et al.   CANCER LETTERS

Low-dose decitabine enhances the effect of PD-1 blockade in colorectal cancer with microsatellite stability by re-modulating the tumor microenvironment

(2018) Ganjun Yu et al.   Cellular & Molecular Immunology

The oncometabolite D-2-hydroxyglutarate is an intercellular mediator in IDH-mutant gliomas that inhibits both complement and T cells

(2018) Lingjun Zhang et al.   CLINICAL CANCER RESEARCH

RNA N6-methyladenosine methyltransferase-like 3 promotes liver cancer progression through YTHDF2-dependent posttranscriptional silencing of SOCS2

(2018) Mengnuo Chen et al.   HEPATOLOGY

4-1BB costimulation induces T cell mitochondrial function and biogenesis enabling cancer immunotherapeutic responses

(2018) Ashley V. Menk et al.   JOURNAL OF EXPERIMENTAL MEDICINE

Metabolic Barriers to T Cell Function in Tumors

(2018) Ayaka Sugiura et al.   JOURNAL OF IMMUNOLOGY

Suppression of antitumor T cell immunity by the oncometabolite (R)-2-hydroxyglutarate

(2018) Lukas Bunse et al.   NATURE MEDICINE

The Key Role of Epigenetics in Human Disease Prevention and Mitigation

(2018) Andrew P. Feinberg   NEW ENGLAND JOURNAL OF MEDICINE

DOT1L inhibition attenuates graft-versus-host disease by allogeneic T cells in adoptive immunotherapy models

(2018) Yuki Kagoya et al.   Nature Communications

Carnitine Palmitoyltransferase 1A Has a Lysine Succinyltransferase Activity

(2018) Kiran Kurmi et al.   Cell Reports

Loss of Dnmt3a Immortalizes Hematopoietic Stem Cells In Vivo

(2018) Mira Jeong et al.   Cell Reports

Modulation of EZH2 expression in T cells improves efficacy of anti–CTLA-4 therapy

(2018) Sangeeta Goswami et al.   JOURNAL OF CLINICAL INVESTIGATION

Disruption of TET2 promotes the therapeutic efficacy of CD19-targeted T cells

(2018) Joseph A. Fraietta et al.   NATURE

BET Bromodomain Inhibition Cooperates with PD-1 Blockade to Facilitate Antitumor Response inKras-Mutant Non–Small Cell Lung Cancer

(2018) Dennis O. Adeegbe et al.   Cancer Immunology Research

Lactate: A Metabolic Driver in the Tumour Landscape

(2018) Luigi Ippolito et al.   TRENDS IN BIOCHEMICAL SCIENCES

Metabolic reprogramming of human CD8+memory T cells through loss of SIRT1

(2017) Mark Y. Jeng et al.   JOURNAL OF EXPERIMENTAL MEDICINE

KAT2A coupled with the α-KGDH complex acts as a histone H3 succinyltransferase

(2017) Yugang Wang et al.   NATURE

Survival of tissue-resident memory T cells requires exogenous lipid uptake and metabolism

(2017) Youdong Pan et al.   NATURE

The immune contexture in cancer prognosis and treatment

(2017) Wolf H. Fridman et al.   Nature Reviews Clinical Oncology

Dual-specificity phosphatase 5 controls the localized inhibition, propagation, and transforming potential of ERK signaling

(2017) Andrew M. Kidger et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Synergistic Immunostimulatory Effects and Therapeutic Benefit of Combined Histone Deacetylase and Bromodomain Inhibition in Non–Small Cell Lung Cancer

(2017) Dennis O. Adeegbe et al.   Cancer Discovery

The Histone Methyltransferase Ezh2 Controls Mechanisms of Adaptive Resistance to Tumor Immunotherapy

(2017) Daniel Zingg et al.   Cell Reports

BET-Bromodomain Inhibitors Engage the Host Immune System and Regulate Expression of the Immune Checkpoint Ligand PD-L1

(2017) Simon J. Hogg et al.   Cell Reports

CD137 (4-1BB) Costimulation Modifies DNA Methylation in CD8 + T Cell–Relevant Genes

(2017) M. Angela Aznar et al.   Cancer Immunology Research

Bromodomain inhibition exerts its therapeutic potential in malignant pleural mesothelioma by promoting immunogenic cell death and changing the tumor immune-environment

(2017) Chiara Riganti et al.   OncoImmunology

T Cell Cancer Therapy Requires CD40-CD40L Activation of Tumor Necrosis Factor and Inducible Nitric-Oxide-Synthase-Producing Dendritic Cells

(2016) Ilaria Marigo et al.   CANCER CELL

L-Arginine Modulates T Cell Metabolism and Enhances Survival and Anti-tumor Activity

(2016) Roger Geiger et al.   CELL

AMPK/Snf1 signaling regulates histone acetylation: Impact on gene expression and epigenetic functions

(2016) Antero Salminen et al.   CELLULAR SIGNALLING

HDAC Inhibitors Enhance T-Cell Chemokine Expression and Augment Response to PD-1 Immunotherapy in Lung Adenocarcinoma

(2016) Hong Zheng et al.   CLINICAL CANCER RESEARCH

Metabolic control of methylation and acetylation

(2016) Xiaoyang Su et al.   CURRENT OPINION IN CHEMICAL BIOLOGY

Bioenergetic Insufficiencies Due to Metabolic Alterations Regulated by the Inhibitory Receptor PD-1 Are an Early Driver of CD8 + T Cell Exhaustion

(2016) Bertram Bengsch et al.   IMMUNITY

BET bromodomain inhibition enhances T cell persistence and function in adoptive immunotherapy models

(2016) Yuki Kagoya et al.   JOURNAL OF CLINICAL INVESTIGATION

Tumour hypoxia causes DNA hypermethylation by reducing TET activity

(2016) Bernard Thienpont et al.   NATURE

Potentiating the antitumour response of CD8+ T cells by modulating cholesterol metabolism

(2016) Wei Yang et al.   NATURE

Ionic immune suppression within the tumour microenvironment limits T cell effector function

(2016) Robert Eil et al.   NATURE

S-2-hydroxyglutarate regulates CD8+ T-lymphocyte fate

(2016) Petros A. Tyrakis et al.   NATURE

Aerobic glycolysis promotes T helper 1 cell differentiation through an epigenetic mechanism

(2016) M. Peng et al.   SCIENCE

Epigenetic stability of exhausted T cells limits durability of reinvigoration by PD-1 blockade

(2016) K. E. Pauken et al.   SCIENCE

Lipids Reprogram Metabolism to Become a Major Carbon Source for Histone Acetylation

(2016) Eoin McDonnell et al.   Cell Reports

Starved and Asphyxiated: How Can CD8+ T Cells within a Tumor Microenvironment Prevent Tumor Progression

(2016) Ying Zhang et al.   Frontiers in Immunology

Metabolic Competition in the Tumor Microenvironment Is a Driver of Cancer Progression

(2015) Chih-Hao Chang et al.   CELL

Hypoxia Induces Production of L-2-Hydroxyglutarate

(2015) Andrew M. Intlekofer et al.   Cell Metabolism

Lineage relationship of CD8+ T cell subsets is revealed by progressive changes in the epigenetic landscape

(2015) Joseph G. Crompton et al.   Cellular & Molecular Immunology

Myeloid-derived suppressor cells in the tumor microenvironment: expect the unexpected

(2015) Douglas Marvel et al.   JOURNAL OF CLINICAL INVESTIGATION

Cancer mediates effector T cell dysfunction by targeting microRNAs and EZH2 via glycolysis restriction

(2015) Ende Zhao et al.   NATURE IMMUNOLOGY

DUSP10 regulates intestinal epithelial cell growth and colorectal tumorigenesis

(2015) C W Png et al.   ONCOGENE

CRISPR/Cas9 somatic multiplex-mutagenesis for high-throughput functional cancer genomics in mice

(2015) Julia Weber et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Decitabine Enhances Lymphocyte Migration and Function and Synergizes with CTLA-4 Blockade in a Murine Ovarian Cancer Model

(2015) L. Wang et al.   Cancer Immunology Research

HDAC Inhibition Upregulates PD-1 Ligands in Melanoma and Augments Immunotherapy with PD-1 Blockade

(2015) D. M. Woods et al.   Cancer Immunology Research

miR-155 augments CD8+T-cell antitumor activity in lymphoreplete hosts by enhancing responsiveness to homeostatic γccytokines

(2014) Yun Ji et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

T-bet and Eomes Are Differentially Linked to the Exhausted Phenotype of CD8+ T Cells in HIV Infection

(2014) Marcus Buggert et al.   PLoS Pathogens

The histone deacetylase inhibitor, LBH589, promotes the systemic cytokine and effector responses of adoptively transferred CD8+ T cells

(2014) Dominique N Lisiero et al.   Journal for ImmunoTherapy of Cancer

Succinate: A New Epigenetic Hacker

(2013) Ming Yang et al.   CANCER CELL

Nitric Oxide Modifies Global Histone Methylation by Inhibiting Jumonji C Domain-containing Demethylases

(2013) Jason R. Hickok et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Epigenetic Regulation of Autophagy by the Methyltransferase G9a

(2013) A. Artal-Martinez de Narvajas et al.   MOLECULAR AND CELLULAR BIOLOGY

IDH mutation impairs histone demethylation and results in a block to cell differentiation

(2012) Chao Lu et al.   NATURE

Enhanced Antitumor Activity Induced by Adoptive T-Cell Transfer and Adjunctive Use of the Histone Deacetylase Inhibitor LAQ824

(2009) D. D. Vo et al.   CANCER RESEARCH

Cancer-associated IDH1 mutations produce 2-hydroxyglutarate

(2009) Lenny Dang et al.   NATURE

ATP-Citrate Lyase Links Cellular Metabolism to Histone Acetylation

(2009) K. E. Wellen et al.   SCIENCE