TIM-3 as a Target for Cancer Immunotherapy and Mechanisms of Action

Tissue Tregs

(2016) Marisella Panduro et al.   Annual Review of Immunology

Perinatal Licensing of Thermogenesis by IL-33 and ST2

(2016) Justin I. Odegaard et al.   CELL

Lag-3, Tim-3, and TIGIT: Co-inhibitory Receptors with Specialized Functions in Immune Regulation

(2016) Ana C. Anderson et al.   IMMUNITY

CD163 + M2-type tumor-associated macrophage support the suppression of tumor-infiltrating T cells in osteosarcoma

(2016) Qinglin Han et al.   INTERNATIONAL IMMUNOPHARMACOLOGY

Targeting PD-1 and Tim-3 Pathways to Reverse CD8 T-Cell Exhaustion and Enhance Ex Vivo T-Cell Responses to Autologous Dendritic/Tumor Vaccines

(2016) Jingwei Liu et al.   JOURNAL OF IMMUNOTHERAPY

Adaptive resistance to therapeutic PD-1 blockade is associated with upregulation of alternative immune checkpoints

(2016) Shohei Koyama et al.   Nature Communications

Expression of immune checkpoints in T cells of esophageal cancer patients

(2016) Jinhua Xie et al.   Oncotarget

TIM-3 Regulates Distinct Functions in Macrophages

(2016) Ranferi Ocaña-Guzman et al.   Frontiers in Immunology

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

Tim-3 expression in tumour-associated macrophages: a new player in HCC progression

(2015) Tobias Flecken et al.   GUT

Tim-3 fosters HCC development by enhancing TGF-β-mediated alternative activation of macrophages

(2015) Wenjiang Yan et al.   GUT

Five-Year Survival Rates for Treatment-Naive Patients With Advanced Melanoma Who Received Ipilimumab Plus Dacarbazine in a Phase III Trial

(2015) Michele Maio et al.   JOURNAL OF CLINICAL ONCOLOGY

Pooled Analysis of Long-Term Survival Data From Phase II and Phase III Trials of Ipilimumab in Unresectable or Metastatic Melanoma

(2015) Dirk Schadendorf et al.   JOURNAL OF CLINICAL ONCOLOGY

Tim-3 enhances FcεRI-proximal signaling to modulate mast cell activation

(2015) Binh L. Phong et al.   JOURNAL OF EXPERIMENTAL MEDICINE

PD-1 Blockade in Tumors with Mismatch-Repair Deficiency

(2015) Dung T. Le et al.   NEW ENGLAND JOURNAL OF MEDICINE

Pembrolizumab for the Treatment of Non–Small-Cell Lung Cancer

(2015) Edward B. Garon et al.   NEW ENGLAND JOURNAL OF MEDICINE

Nivolumab versus Docetaxel in Advanced Squamous-Cell Non–Small-Cell Lung Cancer

(2015) Julie Brahmer et al.   NEW ENGLAND JOURNAL OF MEDICINE

PD-1 Blockade with Nivolumab in Relapsed or Refractory Hodgkin's Lymphoma

(2015) Stephen M. Ansell et al.   NEW ENGLAND JOURNAL OF MEDICINE

Nivolumab versus Everolimus in Advanced Renal-Cell Carcinoma

(2015) Robert J. Motzer et al.   NEW ENGLAND JOURNAL OF MEDICINE

Pembrolizumab versus Ipilimumab in Advanced Melanoma

(2015) Caroline Robert et al.   NEW ENGLAND JOURNAL OF MEDICINE

Combined Nivolumab and Ipilimumab or Monotherapy in Untreated Melanoma

(2015) James Larkin et al.   NEW ENGLAND JOURNAL OF MEDICINE

Ipilimumab-dependent cell-mediated cytotoxicity of regulatory T cells ex vivo by nonclassical monocytes in melanoma patients

(2015) Emanuela Romano et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Tim-3 expression represents dysfunctional tumor infiltrating T cells in renal cell carcinoma

(2015) Chen Cai et al.   WORLD JOURNAL OF UROLOGY

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

Effect of TIM-3 Blockade on the Immunophenotype and Cytokine Profile of Murine Uterine NK Cells

(2015) Sudipta Tripathi et al.   PLoS One

TIM-3 Suppresses Anti-CD3/CD28-Induced TCR Activation and IL-2 Expression through the NFAT Signaling Pathway

(2015) Brian Tomkowicz et al.   PLoS One

Lack of TIM-3 Immunoregulation in Multiple Sclerosis

(2014) L. Yang et al.   JOURNAL OF IMMUNOLOGY

Immunoregulation of Dendritic Cells by the Receptor T cell Ig and Mucin Protein-3 via Bruton’s Tyrosine Kinase and c-Src

(2014) Neeraj Maurya et al.   JOURNAL OF IMMUNOLOGY

Antigen Receptor Kinase Two-Step

(2014) Lawrence P. Kane   JOURNAL OF IMMUNOLOGY

Too Much of a Good Thing? Tim-3 and TCR Signaling in T Cell Exhaustion

(2014) Robert L. Ferris et al.   JOURNAL OF IMMUNOLOGY

Tim-3 Directly Enhances CD8 T Cell Responses to Acute Listeria monocytogenes Infection

(2014) J. V. Gorman et al.   JOURNAL OF IMMUNOLOGY

CEACAM1 regulates TIM-3-mediated tolerance and exhaustion

(2014) Yu-Hwa Huang et al.   NATURE

The alarmin IL-33 promotes regulatory T-cell function in the intestine

(2014) Chris Schiering et al.   NATURE

Tim-3 Negatively Mediates Natural Killer Cell Function in LPS-Induced Endotoxic Shock

(2014) Hongyan Hou et al.   PLoS One

Reversal of NK-Cell Exhaustion in Advanced Melanoma by Tim-3 Blockade

(2014) I. P. da Silva et al.   Cancer Immunology Research

Reversal of natural killer cell exhaustion by TIM-3 blockade

(2014) Anne Gallois et al.   OncoImmunology

Intratumoral regulatory T cells upregulate immunosuppressive molecules in head and neck cancer patients

(2013) H-B Jie et al.   BRITISH JOURNAL OF CANCER

A Special Population of Regulatory T Cells Potentiates Muscle Repair

(2013) Dalia Burzyn et al.   CELL

T Cell Ig Mucin-3 Promotes Homeostasis of Sepsis by Negatively Regulating the TLR Response

(2013) X. Yang et al.   JOURNAL OF IMMUNOLOGY

T Cell Ig and Mucin Domain-Containing Protein 3 Is Recruited to the Immune Synapse, Disrupts Stable Synapse Formation, and Associates with Receptor Phosphatases

(2013) K. L. Clayton et al.   JOURNAL OF IMMUNOLOGY

IL-1  Promotes Antimicrobial Immunity in Macrophages by Regulating TNFR Signaling and Caspase-3 Activation

(2013) P. Jayaraman et al.   JOURNAL OF IMMUNOLOGY

Nivolumab plus Ipilimumab in Advanced Melanoma

(2013) Jedd D. Wolchok et al.   NEW ENGLAND JOURNAL OF MEDICINE

Tim-3 Expression Defines Regulatory T Cells in Human Tumors

(2013) Jing Yan et al.   PLoS One

Anti-CTLA-4 Antibodies of IgG2a Isotype Enhance Antitumor Activity through Reduction of Intratumoral Regulatory T Cells

(2013) M. J. Selby et al.   Cancer Immunology Research

Tim-3: An Activation Marker and Activation Limiter of Innate Immune Cells

(2013) Gencheng Han et al.   Frontiers in Immunology

Tumor-associated macrophages subvert T-cell function and correlate with reduced survival in clear cell renal cell carcinoma

(2013) Stefanie Regine Dannenmann et al.   OncoImmunology

Contrasting acute graft-versus-host disease effects of Tim-3/galectin-9 pathway blockade dependent upon the presence of donor regulatory T cells

(2012) R. G. Veenstra et al.   BLOOD

Tim-3 marks human natural killer cell maturation and suppresses cell-mediated cytotoxicity

(2012) L. C. Ndhlovu et al.   BLOOD

Tim-3 is an inducible human natural killer cell receptor that enhances interferon gamma production in response to galectin-9

(2012) M. K. Gleason et al.   BLOOD

Allograft rejection is restrained by short-lived TIM-3+PD-1+Foxp3+ Tregs

(2012) Shipra Gupta et al.   JOURNAL OF CLINICAL INVESTIGATION

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

The Tim3-Galectin 9 Pathway Induces Antibacterial Activity in Human Macrophages Infected with Mycobacterium tuberculosis

(2012) I. Sada-Ovalle et al.   JOURNAL OF IMMUNOLOGY

Expression and anatomical distribution of TIM-containing molecules in Langerhans cell sarcoma

(2012) Jingwei Li et al.   JOURNAL OF MOLECULAR HISTOLOGY

Tumor immunity times out: TIM-3 and HMGB1

(2012) Daolin Tang et al.   NATURE IMMUNOLOGY

Tumor-infiltrating DCs suppress nucleic acid–mediated innate immune responses through interactions between the receptor TIM-3 and the alarmin HMGB1

(2012) Shigeki Chiba et al.   NATURE IMMUNOLOGY

Bat3 promotes T cell responses and autoimmunity by repressing Tim-3–mediated cell death and exhaustion

(2012) Manu Rangachari et al.   NATURE MEDICINE

Safety and Activity of Anti–PD-L1 Antibody in Patients with Advanced Cancer

(2012) Julie R. Brahmer et al.   NEW ENGLAND JOURNAL OF MEDICINE

Safety, Activity, and Immune Correlates of Anti–PD-1 Antibody in Cancer

(2012) Suzanne L. Topalian et al.   NEW ENGLAND JOURNAL OF MEDICINE

TIM-3 Expression Characterizes Regulatory T Cells in Tumor Tissues and Is Associated with Lung Cancer Progression

(2012) Xin Gao et al.   PLoS One

Anti-TIM3 Antibody Promotes T Cell IFN- -Mediated Antitumor Immunity and Suppresses Established Tumors

(2011) S. F. Ngiow et al.   CANCER RESEARCH

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

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

Tim-3 regulates pro- and anti-inflammatory cytokine expression in human CD14+ monocytes

(2011) Ying Zhang et al.   JOURNAL OF LEUKOCYTE BIOLOGY

Phosphotyrosine-Dependent Coupling of Tim-3 to T-Cell Receptor Signaling Pathways

(2011) J. Lee et al.   MOLECULAR AND CELLULAR BIOLOGY

Ipilimumab plus Dacarbazine for Previously Untreated Metastatic Melanoma

(2011) Caroline Robert et al.   NEW ENGLAND JOURNAL OF MEDICINE

Tim-3 Negatively Regulates IL-12 Expression by Monocytes in HCV Infection

(2011) Ying Zhang et al.   PLoS One

Emerging Tim-3 functions in antimicrobial and tumor immunity

(2011) Kaori Sakuishi et al.   TRENDS IN IMMUNOLOGY

Tim3 binding to galectin-9 stimulates antimicrobial immunity

(2010) Pushpa Jayaraman 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

T cell immunoglobulin- and mucin-domain-containing molecule-3 (Tim-3) mediates natural killer cell suppression in chronic hepatitis B

(2010) Ying Ju et al.   JOURNAL OF HEPATOLOGY

Premature Terminal Exhaustion of Friend Virus-Specific Effector CD8+ T Cells by Rapid Induction of Multiple Inhibitory Receptors

(2010) S. Takamura et al.   JOURNAL OF IMMUNOLOGY

Tim-3/Galectin-9 Pathway: Regulation of Th1 Immunity through Promotion of CD11b+Ly-6G+ Myeloid Cells

(2010) V. Dardalhon et al.   JOURNAL OF IMMUNOLOGY

TIM-3: A Novel Regulatory Molecule of Alloimmune Activation

(2010) O. Boenisch et al.   JOURNAL OF IMMUNOLOGY

T Cell/Transmembrane, Ig, and Mucin-3 Allelic Variants Differentially Recognize Phosphatidylserine and Mediate Phagocytosis of Apoptotic Cells

(2010) Rosemarie H. DeKruyff et al.   JOURNAL OF IMMUNOLOGY

Improved Survival with Ipilimumab in Patients with Metastatic Melanoma

(2010) F. Stephen Hodi et al.   NEW ENGLAND JOURNAL OF MEDICINE

Tim-3 mediates phagocytosis of apoptotic cells and cross-presentation

(2009) M. Nakayama et al.   BLOOD

TIM-3 is expressed on activated human CD4+ T cells and regulates Th1 and Th17 cytokines

(2009) William D. Hastings et al.   EUROPEAN JOURNAL OF IMMUNOLOGY

Negative Immune Regulator Tim-3 Is Overexpressed on T Cells in Hepatitis C Virus Infection and Its Blockade Rescues Dysfunctional CD4+ and CD8+ T Cells

(2009) L. Golden-Mason et al.   JOURNAL OF VIROLOGY

TIMs: central regulators of immune responses: Figure 1.

(2008) David A. Hafler et al.   JOURNAL OF EXPERIMENTAL MEDICINE

Tim-3 expression defines a novel population of dysfunctional T cells with highly elevated frequencies in progressive HIV-1 infection

(2008) R. Brad Jones et al.   JOURNAL OF EXPERIMENTAL MEDICINE