Tumor Microenvironment: A Metabolic Player that Shapes the Immune Response

Mechanisms of resistance to CAR T cell therapy

(2019) Nirali N. Shah et al.   Nature Reviews Clinical Oncology

Cystine–glutamate antiporter xCT deficiency suppresses tumor growth while preserving antitumor immunity

(2019) Michael D. Arensman et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Genetic Ablation of the Cystine Transporter xCT in PDAC Cells Inhibits mTORC1, Growth, Survival, and Tumor Formation via Nutrient and Oxidative Stresses

(2019) Boutaina Daher et al.   CANCER RESEARCH

Epacadostat plus pembrolizumab versus placebo plus pembrolizumab in patients with unresectable or metastatic melanoma (ECHO-301/KEYNOTE-252): a phase 3, randomised, double-blind study

(2019) Georgina V Long et al.   LANCET ONCOLOGY

T Cell Activation Depends on Extracellular Alanine

(2019) Noga Ron-Harel et al.   Cell Reports

Transsulfuration Activity Can Support Cell Growth upon Extracellular Cysteine Limitation

(2019) Jiajun Zhu et al.   Cell Metabolism

Cutting Edge: Elevated Glycolytic Metabolism Limits the Formation of Memory CD8+ T Cells in Early Life

(2019) Cybelle Tabilas et al.   JOURNAL OF IMMUNOLOGY

Metabolic regulation of gene expression by histone lactylation

(2019) Di Zhang et al.   NATURE

Restricting Glycolysis Preserves T Cell Effector Functions and Augments Checkpoint Therapy

(2019) Kathrin Renner et al.   Cell Reports

Metabolic reprogramming enables hepatocarcinoma cells to efficiently adapt and survive to a nutrient-restricted microenvironment

(2018) Shamir Cassim et al.   CELL CYCLE

Human T Cell Development, Localization, and Function throughout Life

(2018) Brahma V. Kumar et al.   IMMUNITY

Understanding the tumor immune microenvironment (TIME) for effective therapy

(2018) Mikhail Binnewies et al.   NATURE MEDICINE

Metabolite profiling identifies a signature of tumorigenicity in hepatocellular carcinoma

(2018) Shamir Cassim et al.   Oncotarget

Anti-PD-1 and Anti-CTLA-4 Therapies in Cancer: Mechanisms of Action, Efficacy, and Limitations

(2018) Judith A. Seidel et al.   Frontiers in Oncology

Double genetic disruption of lactate dehydrogenase A and B is required to ablate the ‘Warburg effect’ restricting tumor growth to oxidative metabolism

(2018) Maša Ždralević et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Macrophage-derived IL-1β and TNF-α regulate arginine metabolism in neuroblastoma

(2018) Livingstone Fultang et al.   CANCER RESEARCH

Tumor immunoevasion via acidosis-dependent induction of regulatory tumor-associated macrophages

(2018) Toszka Bohn et al.   NATURE IMMUNOLOGY

Tumour-elicited neutrophils engage mitochondrial metabolism to circumvent nutrient limitations and maintain immune suppression

(2018) Christopher M. Rice et al.   Nature Communications

Cysteine reactivity across the subcellular universe

(2018) Daniel W Bak et al.   CURRENT OPINION IN CHEMICAL BIOLOGY

Glutathione Primes T Cell Metabolism for Inflammation

(2017) Tak W. Mak et al.   IMMUNITY

Tumor-associated macrophages: from basic research to clinical application

(2017) Li Yang et al.   Journal of Hematology & Oncology

Highly tumorigenic hepatocellular carcinoma cell line with cancer stem cell-like properties

(2017) Benoit Lacoste et al.   PLoS One

Cancer acidity: An ultimate frontier of tumor immune escape and a novel target of immunomodulation

(2017) Veronica Huber et al.   SEMINARS IN CANCER BIOLOGY

The glutamate/cystine xCT antiporter antagonizes glutamine metabolism and reduces nutrient flexibility

(2017) Chun-Shik Shin et al.   Nature Communications

Environmental cystine drives glutamine anaplerosis and sensitizes cancer cells to glutaminase inhibition

(2017) Alexander Muir et al.   eLife

What Fuels Natural Killers? Metabolism and NK Cell Responses

(2017) Clair M. Gardiner et al.   Frontiers in Immunology

Synergistic Transcutaneous Immunotherapy Enhances Antitumor Immune Responses through Delivery of Checkpoint Inhibitors

(2016) Yanqi Ye et al.   ACS Nano

Na + /H + antiporter (NHE1) and lactate/H + symporters (MCTs) in pH homeostasis and cancer metabolism

(2016) Laurent Counillon et al.   BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH

Co-inhibition of CD73 and A2AR Adenosine Signaling Improves Anti-tumor Immune Responses

(2016) Arabella Young et al.   CANCER CELL

Paracrine Induction of HIF by Glutamate in Breast Cancer: EglN1 Senses Cysteine

(2016) Kimberly J. Briggs et al.   CELL

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

(2016) Roger Geiger et al.   CELL

Macrophage Metabolism Controls Tumor Blood Vessel Morphogenesis and Metastasis

(2016) Mathias Wenes et al.   Cell Metabolism

LDHA-Associated Lactic Acid Production Blunts Tumor Immunosurveillance by T and NK Cells

(2016) Almut Brand et al.   Cell Metabolism

Oncometabolites: Unconventional triggers of oncogenic signalling cascades

(2016) Marco Sciacovelli et al.   FREE RADICAL BIOLOGY AND MEDICINE

Fluorescence-based measurement of cystine uptake through xCT shows requirement for ROS detoxification in activated lymphocytes

(2016) Peter J. Siska et al.   JOURNAL OF IMMUNOLOGICAL METHODS

Foxp3 and Toll-like receptor signaling balance Treg cell anabolic metabolism for suppression

(2016) Valerie A Gerriets et al.   NATURE IMMUNOLOGY

Neutrophil extracellular traps enriched in oxidized mitochondrial DNA are interferogenic and contribute to lupus-like disease

(2016) Christian Lood et al.   NATURE MEDICINE

Coming-of-Age of Antibodies in Cancer Therapeutics

(2016) B. Vijayalakshmi Ayyar et al.   TRENDS IN PHARMACOLOGICAL SCIENCES

Neutrophils Suppress Intraluminal NK Cell-Mediated Tumor Cell Clearance and Enhance Extravasation of Disseminated Carcinoma Cells

(2016) A. Spiegel et al.   Cancer Discovery

Human mesenchymal stromal cell-secreted lactate induces M2-macrophage differentiation by metabolic reprogramming

(2016) Silvia Selleri et al.   Oncotarget

Lactate Contribution to the Tumor Microenvironment: Mechanisms, Effects on Immune Cells and Therapeutic Relevance

(2016) Susana Romero-Garcia et al.   Frontiers in Immunology

Metabolic communication in tumors: a new layer of immunoregulation for immune evasion

(2016) Ping-Chih Ho et al.   Journal for ImmunoTherapy of Cancer

Advances in Cancer Immunotherapy in Solid Tumors

(2016) Smitha Menon et al.   Cancers

Targeting arginine metabolism pathway to treat arginine-dependent cancers

(2015) Fuming Qiu et al.   CANCER LETTERS

Human Pancreatic Cancer Tumors Are Nutrient Poor and Tumor Cells Actively Scavenge Extracellular Protein

(2015) J. J. Kamphorst et al.   CANCER RESEARCH

Neutralization of Tumor Acidity Improves Antitumor Responses to Immunotherapy

(2015) Shari Pilon-Thomas et al.   CANCER RESEARCH

Phosphoenolpyruvate Is a Metabolic Checkpoint of Anti-tumor T Cell Responses

(2015) Ping-Chih Ho et al.   CELL

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

(2015) Chih-Hao Chang et al.   CELL

2-Hydroxyglutarate Inhibits ATP Synthase and mTOR Signaling

(2015) Xudong Fu et al.   Cell Metabolism

The Energy Sensor AMPK Regulates T Cell Metabolic Adaptation and Effector Responses In Vivo

(2015) Julianna Blagih et al.   IMMUNITY

Glycolysis controls the induction of human regulatory T cells by modulating the expression of FOXP3 exon 2 splicing variants

(2015) Veronica De Rosa et al.   NATURE IMMUNOLOGY

Glutamine-dependent α-ketoglutarate production regulates the balance between T helper 1 cell and regulatory T cell generation

(2015) Dorota Klysz et al.   Science Signaling

T cell metabolic fitness in antitumor immunity

(2015) Peter J. Siska et al.   TRENDS IN IMMUNOLOGY

Deficiency of AMPK in CD8+ T cells suppresses their anti-tumor function by inducing protein phosphatase-mediated cell death

(2015) Enyu Rao et al.   Oncotarget

Human CD4+ T cells require exogenous cystine for glutathione and DNA synthesis

(2015) Trine B. Levring et al.   Oncotarget

Preventing Allograft Rejection by Targeting Immune Metabolism

(2015) Chen-Fang Lee et al.   Cell Reports

Glutamine-dependent α-ketoglutarate production regulates the balance between T helper 1 cell and regulatory T cell generation

(2015) Dorota Klysz et al.   Science Signaling

Tryptophan-Degrading Enzymes in Tumoral Immune Resistance

(2015) Nicolas van Baren et al.   Frontiers in Immunology

How Neutrophils Shape Adaptive Immune Responses

(2015) Pieter H. C. Leliefeld et al.   Frontiers in Immunology

Genetic Disruption of Lactate/H+ Symporters (MCTs) and Their Subunit CD147/BASIGIN Sensitizes Glycolytic Tumor Cells to Phenformin

(2014) I. Marchiq et al.   CANCER RESEARCH

Antimetastatic Effects of Blocking PD-1 and the Adenosine A2A Receptor

(2014) D. Mittal et al.   CANCER RESEARCH

Regulation of Ferroptotic Cancer Cell Death by GPX4

(2014) Wan Seok Yang et al.   CELL

Phenotypic alterations, clinical impact and therapeutic potential of regulatory T cells in cancer

(2014) Belal Chaudhary et al.   EXPERT OPINION ON BIOLOGICAL THERAPY

Inflammatory T Cell Responses Rely on Amino Acid Transporter ASCT2 Facilitation of Glutamine Uptake and mTORC1 Kinase Activation

(2014) Mako Nakaya et al.   IMMUNITY

Transduction with the Antioxidant Enzyme Catalase Protects Human T Cells against Oxidative Stress

(2014) T. Ando et al.   JOURNAL OF IMMUNOLOGY

mTORC1-Dependent Metabolic Reprogramming Is a Prerequisite for NK Cell Effector Function

(2014) Raymond P. Donnelly et al.   JOURNAL OF IMMUNOLOGY

Impaired T cell function in argininosuccinate synthetase deficiency

(2014) Tatyana N. Tarasenko et al.   JOURNAL OF LEUKOCYTE BIOLOGY

Functional polarization of tumour-associated macrophages by tumour-derived lactic acid

(2014) Oscar R. Colegio et al.   NATURE

The metabolic checkpoint kinase mTOR is essential for IL-15 signaling during the development and activation of NK cells

(2014) Antoine Marçais et al.   NATURE IMMUNOLOGY

From Monocytes to M1/M2 Macrophages: Phenotypical vs. Functional Differentiation

(2014) Paola Italiani et al.   Frontiers in Immunology

Impeding Macrophage Entry into Hypoxic Tumor Areas by Sema3A/Nrp1 Signaling Blockade Inhibits Angiogenesis and Restores Antitumor Immunity

(2013) Andrea Casazza et al.   CANCER CELL

Posttranscriptional Control of T Cell Effector Function by Aerobic Glycolysis

(2013) Chih-Hao Chang et al.   CELL

T cell anergy, exhaustion, senescence, and stemness in the tumor microenvironment

(2013) Joel Crespo et al.   CURRENT OPINION IN IMMUNOLOGY

Mitochondria Are Required for Antigen-Specific T Cell Activation through Reactive Oxygen Species Signaling

(2013) Laura A. Sena et al.   IMMUNITY

Oncometabolites: linking altered metabolism with cancer

(2013) Ming Yang et al.   JOURNAL OF CLINICAL INVESTIGATION

Dendritic Cell Reprogramming by Endogenously Produced Lactic Acid

(2013) A. Nasi et al.   JOURNAL OF IMMUNOLOGY

Tumor-Derived Lactate Modifies Antitumor Immune Response: Effect on Myeloid-Derived Suppressor Cells and NK Cells

(2013) Z. Husain et al.   JOURNAL OF IMMUNOLOGY

Control of amino-acid transport by antigen receptors coordinates the metabolic reprogramming essential for T cell differentiation

(2013) Linda V Sinclair et al.   NATURE IMMUNOLOGY

Blockade of A2Areceptors potently suppresses the metastasis of CD73+tumors

(2013) Paul A. Beavis et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

CD8 memory T cells have a bioenergetic advantage that underlies their rapid recall ability

(2013) G. J. W. van der Windt et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

B cell-regulated immune responses in tumor models and cancer patients

(2013) Carlo Fremd et al.   OncoImmunology

Modulation of Microenvironment Acidity Reverses Anergy in Human and Murine Tumor-Infiltrating T Lymphocytes

(2012) A. Calcinotto et al.   CANCER RESEARCH

Tumor Suppression in the Absence of p53-Mediated Cell-Cycle Arrest, Apoptosis, and Senescence

(2012) Tongyuan Li et al.   CELL

Ferroptosis: An Iron-Dependent Form of Nonapoptotic Cell Death

(2012) Scott J. Dixon et al.   CELL

Metabolic switching and fuel choice during T-cell differentiation and memory development

(2012) Gerritje J. W. Windt et al.   IMMUNOLOGICAL REVIEWS

Macrophage plasticity and polarization: in vivo veritas

(2012) Antonio Sica et al.   JOURNAL OF CLINICAL INVESTIGATION

Cystine/glutamic acid transporter is a novel marker for predicting poor survival in patients with hepatocellular carcinoma

(2012) HIROKI KINOSHITA et al.   ONCOLOGY REPORTS

Metabolic pathways in T cell fate and function

(2012) Valerie A. Gerriets et al.   TRENDS IN IMMUNOLOGY

The HIF-1α Hypoxia Response in Tumor-Infiltrating T Lymphocytes Induces Functional CD137 (4-1BB) for Immunotherapy

(2012) Asís Palazón et al.   Cancer Discovery

Activated human CD4+ T cells express transporters for both cysteine and cystine

(2012) Trine Bøegh Levring et al.   Scientific Reports

Control of TH17/Treg Balance by Hypoxia-Inducible Factor 1

(2011) Eric V. Dang et al.   CELL

Hallmarks of Cancer: The Next Generation

(2011) Douglas Hanahan et al.   CELL

Adenosine promotes alternative macrophage activation via A2A and A2B receptors

(2011) Balázs Csóka et al.   FASEB JOURNAL

The Transcription Factor Myc Controls Metabolic Reprogramming upon T Lymphocyte Activation

(2011) Ruoning Wang et al.   IMMUNITY

The monocarboxylate transporter family-Structure and functional characterization

(2011) Andrew P. Halestrap   IUBMB LIFE

Cutting Edge: Distinct Glycolytic and Lipid Oxidative Metabolic Programs Are Essential for Effector and Regulatory CD4+ T Cell Subsets

(2011) R. D. Michalek et al.   JOURNAL OF IMMUNOLOGY

Evolution of Tumor Metabolism might Reflect Carcinogenesis as a Reverse Evolution process (Dismantling of Multicellularity)

(2011) Khalid O. Alfarouk et al.   Cancers

Differential Dependence on Cysteine from Transsulfuration versus Transport During T Cell Activation

(2010) Sanjay K. Garg et al.   ANTIOXIDANTS & REDOX SIGNALING

Molecular profiling to identify relevant immune resistance mechanisms in the tumor microenvironment

(2010) Thomas F Gajewski et al.   CURRENT OPINION IN IMMUNOLOGY

The metabolic life and times of a T-cell

(2010) Ryan D. Michalek et al.   IMMUNOLOGICAL REVIEWS

Neutrophils: key mediators of tumour angiogenesis

(2010) Simon Tazzyman et al.   INTERNATIONAL JOURNAL OF EXPERIMENTAL PATHOLOGY

Tumour hypoxia induces a metabolic shift causing acidosis: a common feature in cancer

(2010) Johanna Chiche et al.   JOURNAL OF CELLULAR AND MOLECULAR MEDICINE

Glutamine Uptake and Metabolism Are Coordinately Regulated by ERK/MAPK during T Lymphocyte Activation

(2010) E. L. Carr et al.   JOURNAL OF IMMUNOLOGY

Vitamin D controls T cell antigen receptor signaling and activation of human T cells

(2010) Marina Rode von Essen et al.   NATURE IMMUNOLOGY

Lactate Boosts TLR4 Signaling and NF- B Pathway-Mediated Gene Transcription in Macrophages via Monocarboxylate Transporters and MD-2 Up-Regulation

(2009) D. J. Samuvel et al.   JOURNAL OF IMMUNOLOGY

Lactic Acid and Acidification Inhibit TNF Secretion and Glycolysis of Human Monocytes

(2009) K. Dietl et al.   JOURNAL OF IMMUNOLOGY

Extracellular redox modulation by regulatory T cells

(2009) Zhonghua Yan et al.   Nature Chemical Biology

Expression of cystathionine β-synthase is downregulated in hepatocellular carcinoma and associated with poor prognosis

(2009) Kim   ONCOLOGY REPORTS

Halofuginone Inhibits TH17 Cell Differentiation by Activating the Amino Acid Starvation Response

(2009) M. S. Sundrud et al.   SCIENCE

Central role of Sp1-regulated CD39 in hypoxia/ischemia protection

(2008) H. K. Eltzschig et al.   BLOOD

Tumor Cell Metabolism: Cancer's Achilles' Heel

(2008) Guido Kroemer et al.   CANCER CELL

The Biology of Cancer: Metabolic Reprogramming Fuels Cell Growth and Proliferation

(2008) Ralph J. DeBerardinis et al.   Cell Metabolism

Glucose deprivation inhibits multiple key gene expression events and effector functions in CD8+ T cells

(2008) Candace M. Cham et al.   EUROPEAN JOURNAL OF IMMUNOLOGY

The xc− cystine/glutamate antiporter: A potential target for therapy of cancer and other diseases

(2008) Maisie Lo et al.   JOURNAL OF CELLULAR PHYSIOLOGY

Immune escape as a fundamental trait of cancer: focus on IDO

(2008) G C Prendergast   ONCOGENE

Myc regulates a transcriptional program that stimulates mitochondrial glutaminolysis and leads to glutamine addiction

(2008) D. R. Wise et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Chronic inflammation that facilitates tumor progression creates local immune suppression by inducing indoleamine 2,3 dioxygenase

(2008) A. J. Muller et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA