Exhaustion and senescence: two crucial dysfunctional states of T cells in the tumor microenvironment

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

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

Cholesterol Induces CD8+ T Cell Exhaustion in the Tumor Microenvironment

(2019) Xingzhe Ma et al.   Cell Metabolism

TOX transcriptionally and epigenetically programs CD8+ T cell exhaustion

(2019) Omar Khan et al.   NATURE

PD-1 signaling affects cristae morphology and leads to mitochondrial dysfunction in human CD8+ T lymphocytes

(2019) Jesús Ogando et al.   Journal for ImmunoTherapy of Cancer

T Cell Dysfunction in Cancer

(2018) Daniela S. Thommen et al.   CANCER CELL

Increased Tumor Glycolysis Characterizes Immune Resistance to Adoptive T Cell Therapy

(2018) Tina Cascone et al.   Cell Metabolism

T-Cell Exhaustion Signatures Vary with Tumor Type and Are Severe in Glioblastoma

(2018) Karolina Woroniecka et al.   CLINICAL CANCER RESEARCH

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 exhaustion in infection, cancer and autoimmunity

(2018) E. F. McKinney et al.   NATURE IMMUNOLOGY

Metabolic Control of CD8 + T Cell Fate Decisions and Antitumor Immunity

(2018) Lianjun Zhang et al.   TRENDS IN MOLECULAR MEDICINE

TLR8-Mediated Metabolic Control of Human Treg Function: A Mechanistic Target for Cancer Immunotherapy

(2018) Lingyun Li et al.   Cell Metabolism

The EGR2 targets LAG-3 and 4-1BB describe and regulate dysfunctional antigen-specific CD8 + T cells in the tumor microenvironment

(2017) Jason B. Williams et al.   JOURNAL OF EXPERIMENTAL MEDICINE

Transcriptional and epigenetic regulation of T cell hyporesponsiveness

(2017) Renata M. Pereira et al.   JOURNAL OF LEUKOCYTE BIOLOGY

Senescent cells: an emerging target for diseases of ageing

(2017) Bennett G. Childs et al.   NATURE REVIEWS DRUG DISCOVERY

Exhaustion-associated regulatory regions in CD8+tumor-infiltrating T cells

(2017) Giuliana P. Mognol et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

T cell costimulatory receptor CD28 is a primary target for PD-1–mediated inhibition

(2017) Enfu Hui et al.   SCIENCE

Rescue of exhausted CD8 T cells by PD-1–targeted therapies is CD28-dependent

(2017) Alice O. Kamphorst et al.   SCIENCE

A Distinct Gene Module for Dysfunction Uncoupled from Activation in Tumor-Infiltrating T Cells

(2016) Meromit Singer et al.   CELL

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

(2016) Almut Brand et al.   Cell Metabolism

MLL1 is essential for the senescence-associated secretory phenotype

(2016) Brian C. Capell et al.   GENES & DEVELOPMENT

The Tumor Microenvironment Represses T Cell Mitochondrial Biogenesis to Drive Intratumoral T Cell Metabolic Insufficiency and Dysfunction

(2016) Nicole E. Scharping et al.   IMMUNITY

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

Coinhibitory Pathways in the B7-CD28 Ligand-Receptor Family

(2016) Frank A. Schildberg et al.   IMMUNITY

Functional exhaustion of CD4+T cells induced by co-stimulatory signals from myeloid leukaemia cells

(2016) Didem Ozkazanc et al.   IMMUNOLOGY

Senescent Carcinoma-Associated Fibroblasts Upregulate IL8 to Enhance Prometastatic Phenotypes

(2016) Tao Wang et al.   MOLECULAR CANCER RESEARCH

Defining CD8+ T cells that provide the proliferative burst after PD-1 therapy

(2016) Se Jin Im et al.   NATURE

Molecular and Biochemical Aspects of the PD-1 Checkpoint Pathway

(2016) Vassiliki A. Boussiotis   NEW ENGLAND JOURNAL OF MEDICINE

The epigenetic landscape of T cell exhaustion

(2016) D. R. Sen et al.   SCIENCE

PD-L1 (B7-H1) and PD-1 pathway blockade for cancer therapy: Mechanisms, response biomarkers, and combinations

(2016) Weiping Zou et al.   Science Translational Medicine

Senescence of T Lymphocytes: Implications for Enhancing Human Immunity

(2016) Arne N. Akbar et al.   TRENDS IN IMMUNOLOGY

Effector, Memory, and Dysfunctional CD8+T Cell Fates in the Antitumor Immune Response

(2016) John Reiser et al.   Journal of Immunology Research

The PD1:PD-L1/2 Pathway from Discovery to Clinical Implementation

(2016) Kankana Bardhan et al.   Frontiers in Immunology

Immune Checkpoint Blockade: A Common Denominator Approach to Cancer Therapy

(2015) Suzanne L. Topalian et al.   CANCER CELL

Dysfunction of PSA-specific CD8+ T cells in prostate cancer patients correlates with CD38 and Tim-3 expression

(2015) Alberto Sada Japp et al.   CANCER IMMUNOLOGY IMMUNOTHERAPY

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

Immune Checkpoint Targeting in Cancer Therapy: Toward Combination Strategies with Curative Potential

(2015) Padmanee Sharma et al.   CELL

The Transcription Factor NFAT Promotes Exhaustion of Activated CD8 + T Cells

(2015) Gustavo J. Martinez et al.   IMMUNITY

TIGIT and PD-1 impair tumor antigen–specific CD8+ T cells in melanoma patients

(2015) Joe-Marc Chauvin 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

Metabolic control of regulatory T cell development and function

(2015) Hu Zeng et al.   TRENDS IN IMMUNOLOGY

Overcoming T cell exhaustion in infection and cancer

(2015) Kristen E. Pauken et al.   TRENDS IN IMMUNOLOGY

PD-1 alters T-cell metabolic reprogramming by inhibiting glycolysis and promoting lipolysis and fatty acid oxidation

(2015) Nikolaos Patsoukis et al.   Nature Communications

CD39 Expression Identifies Terminally Exhausted CD8+ T Cells

(2015) Prakash K. Gupta et al.   PLoS Pathogens

Progression of Lung Cancer Is Associated with Increased Dysfunction of T Cells Defined by Coexpression of Multiple Inhibitory Receptors

(2015) D. S. Thommen et al.   Cancer Immunology Research

Controlling T cell senescence in the tumor microenvironment for tumor immunotherapy

(2015) Jian Ye et al.   OncoImmunology

TLR8 signaling enhances tumor immunity by preventing tumor-induced T-cell senescence

(2014) J. Ye et al.   EMBO Molecular Medicine

p38 signaling inhibits mTORC1-independent autophagy in senescent human CD8+ T cells

(2014) Sian M. Henson et al.   JOURNAL OF CLINICAL INVESTIGATION

The kinase p38 activated by the metabolic regulator AMPK and scaffold TAB1 drives the senescence of human T cells

(2014) Alessio Lanna et al.   NATURE IMMUNOLOGY

Metabolic Regulation of T Lymphocytes

(2013) Nancie J. MacIver et al.   Annual Review of Immunology

The presence of programmed death 1 (PD-1)-positive tumor-infiltrating lymphocytes is associated with poor prognosis in human breast cancer

(2013) S. Muenst et al.   BREAST CANCER RESEARCH AND TREATMENT

Dual Blockade of PD-1 and CTLA-4 Combined with Tumor Vaccine Effectively Restores T-Cell Rejection Function in Tumors

(2013) J. Duraiswamy et al.   CANCER RESEARCH

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

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

Antitumor CD8+T cells in hepatocellular carcinoma: Present but exhausted

(2013) Ka-Kit Li et al.   HEPATOLOGY

Tumor-Derived    Regulatory T Cells Suppress Innate and Adaptive Immunity through the Induction of Immunosenescence

(2013) J. Ye et al.   JOURNAL OF IMMUNOLOGY

Magnetic resonance imaging of tumor glycolysis using hyperpolarized 13C-labeled glucose

(2013) Tiago B Rodrigues et al.   NATURE MEDICINE

Metabolic Reprogramming and Validation of Hyperpolarized13C Lactate as a Prostate Cancer Biomarker Using a Human Prostate Tissue Slice Culture Bioreactor

(2013) Kayvan R. Keshari et al.   PROSTATE

Tolerance and exhaustion: defining mechanisms of T cell dysfunction

(2013) Andrea Schietinger et al.   TRENDS IN IMMUNOLOGY

Human regulatory T cells induce T-lymphocyte senescence

(2012) J. Ye et al.   BLOOD

Tim-3/galectin-9 signaling pathway mediates T-cell dysfunction and predicts poor prognosis in patients with hepatitis B virus-associated hepatocellular carcinoma

(2012) Hang Li et al.   HEPATOLOGY

IL-12 upregulates TIM-3 expression and induces T cell exhaustion in patients with follicular B cell non-Hodgkin lymphoma

(2012) Zhi-Zhang Yang et al.   JOURNAL OF CLINICAL INVESTIGATION

Progenitor and Terminal Subsets of CD8+ T Cells Cooperate to Contain Chronic Viral Infection

(2012) M. A. Paley et al.   SCIENCE

The three main stumbling blocks for anticancer T cells

(2012) Lukas Baitsch et al.   TRENDS IN IMMUNOLOGY

Coexpression of Tim-3 and PD-1 identifies a CD8+ T-cell exhaustion phenotype in mice with disseminated acute myelogenous leukemia

(2011) Q. Zhou et al.   BLOOD

CD8+ T Cells Specific for Tumor Antigens Can Be Rendered Dysfunctional by the Tumor Microenvironment through Upregulation of the Inhibitory Receptors BTLA and PD-1

(2011) J. Fourcade et al.   CANCER RESEARCH

Lactate Influx through the Endothelial Cell Monocarboxylate Transporter MCT1 Supports an NF- B/IL-8 Pathway that Drives Tumor Angiogenesis

(2011) F. Vegran et al.   CANCER RESEARCH

p38MAPK is a novel DNA damage response-independent regulator of the senescence-associated secretory phenotype

(2011) Adam Freund et al.   EMBO JOURNAL

Exhaustion of tumor-specific CD8+ T cells in metastases from melanoma patients

(2011) Lukas Baitsch et al.   JOURNAL OF CLINICAL INVESTIGATION

T cell exhaustion

(2011) E John Wherry   NATURE IMMUNOLOGY

The Senescence-Associated Secretory Phenotype: The Dark Side of Tumor Suppression

(2010) Jean-Philippe Coppé et al.   Annual Review of Pathology-Mechanisms of Disease

Clinical significance of regulatory T cells and CD8+ effector populations in patients with human endometrial carcinoma

(2010) Wen-Chun Chang et al.   CANCER

Metabolism in T cell activation and differentiation

(2010) Erika L Pearce   CURRENT OPINION IN IMMUNOLOGY

Profound elevation of CD8+ T cells expressing the intraepithelial lymphocyte marker CD103 (αE/β7 Integrin) in high-grade serous ovarian cancer

(2010) John R. Webb et al.   GYNECOLOGIC ONCOLOGY

DNA-SCARS: distinct nuclear structures that sustain damage-induced senescence growth arrest and inflammatory cytokine secretion

(2010) F. Rodier et al.   JOURNAL OF CELL SCIENCE

Lymphoma endothelium preferentially expresses Tim-3 and facilitates the progression of lymphoma by mediating immune evasion

(2010) Xiaoyuan Huang et al.   JOURNAL OF EXPERIMENTAL MEDICINE

Upregulation of Tim-3 and PD-1 expression is associated with tumor antigen–specific CD8+T cell dysfunction in melanoma patients

(2010) Julien Fourcade et al.   JOURNAL OF EXPERIMENTAL MEDICINE

Targeting Tim-3 and PD-1 pathways to reverse T cell exhaustion and restore anti-tumor immunity

(2010) Kaori Sakuishi et al.   JOURNAL OF EXPERIMENTAL MEDICINE

Transcriptional analysis of HIV-specific CD8+ T cells shows that PD-1 inhibits T cell function by upregulating BATF

(2010) Michael Quigley et al.   NATURE MEDICINE

Tumor-infiltrating NY-ESO-1–specific CD8+T cells are negatively regulated by LAG-3 and PD-1 in human ovarian cancer

(2010) Junko Matsuzaki et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Tumor antigen-specific CD8 T cells infiltrating the tumor express high levels of PD-1 and are functionally impaired

(2009) M. Ahmadzadeh et al.   BLOOD

p38α and p38γ Mediate Oncogenicras-induced Senescence through Differential Mechanisms

(2009) Jinny Kwong et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Persistent DNA damage signalling triggers senescence-associated inflammatory cytokine secretion

(2009) Francis Rodier et al.   NATURE CELL BIOLOGY

Vaccination in the elderly: an immunological perspective

(2009) Wilbur H. Chen et al.   TRENDS IN IMMUNOLOGY

CD28− T cells: their role in the age-associated decline of immune function

(2009) Nan-ping Weng et al.   TRENDS IN IMMUNOLOGY

Tumor-Induced Senescent T Cells with Suppressor Function: A Potential Form of Tumor Immune Evasion

(2008) C. L. Montes et al.   CANCER RESEARCH

Oncogene-Induced Senescence Relayed by an Interleukin-Dependent Inflammatory Network

(2008) Thomas Kuilman et al.   CELL

Chemokine Signaling via the CXCR2 Receptor Reinforces Senescence

(2008) Juan C. Acosta et al.   CELL

Hypoxia-Adenosinergic Immunosuppression: Tumor Protection by T Regulatory Cells and Cancerous Tissue Hypoxia

(2008) M. V. Sitkovsky et al.   CLINICAL CANCER RESEARCH

Coregulation of CD8+ T cell exhaustion by multiple inhibitory receptors during chronic viral infection

(2008) Shawn D Blackburn et al.   NATURE IMMUNOLOGY

The tumor microenvironment and its role in promoting tumor growth

(2008) T L Whiteside   ONCOGENE