Promising Targets for Cancer Immunotherapy: TLRs, RLRs, and STING-Mediated Innate Immune Pathways

Activation of the MDA-5–IPS-1 Viral Sensing Pathway Induces Cancer Cell Death and Type I IFN-Dependent Antitumor Immunity

(2016) Xiaofei Yu et al.   CANCER RESEARCH

Agonist-Mediated Activation of STING Induces Apoptosis in Malignant B Cells

(2016) Chih-Hang Anthony Tang et al.   CANCER RESEARCH

STING Promotes the Growth of Tumors Characterized by Low Antigenicity via IDO Activation

(2016) Henrique Lemos et al.   CANCER RESEARCH

Stimulator of interferon genes (STING): A “new chapter” in virus-associated cancer research. Lessons from wild-derived mouse models of innate immunity

(2016) Alexander Poltorak et al.   CYTOKINE & GROWTH FACTOR REVIEWS

Ubiquitination of the Transcription Factor IRF-3 Activates RIPA, the Apoptotic Pathway that Protects Mice from Viral Pathogenesis

(2016) Saurabh Chattopadhyay et al.   IMMUNITY

Application potential of toll-like receptors in cancer immunotherapy

(2016) Ming Shi et al.   MEDICINE

Carcinoma–astrocyte gap junctions promote brain metastasis by cGAMP transfer

(2016) Qing Chen et al.   NATURE

Eradication of large established tumors in mice by combination immunotherapy that engages innate and adaptive immune responses

(2016) Kelly D Moynihan et al.   NATURE MEDICINE

Cancer therapies activate RIG-I-like receptor pathway through endogenous non-coding RNAs

(2016) Diana Rose E. Ranoa et al.   Oncotarget

Antitumor Activity of cGAMP via Stimulation of cGAS-cGAMP-STING-IRF3 Mediated Innate Immune Response

(2016) Tiejun Li et al.   Scientific Reports

The Role of Toll-Like Receptors in Hematopoietic Malignancies

(2016) Darlene A. Monlish et al.   Frontiers in Immunology

Innate Immune Recognition of Cancer

(2015) Seng-Ryong Woo et al.   Annual Review of Immunology

STING activator c-di-GMP enhances the anti-tumor effects of peptide vaccines in melanoma-bearing mice

(2015) Zili Wang et al.   CANCER IMMUNOLOGY IMMUNOTHERAPY

Viral RNA detection by RIG-I-like receptors

(2015) Mitsutoshi Yoneyama et al.   CURRENT OPINION IN IMMUNOLOGY

MAP1S Protein Regulates the Phagocytosis of Bacteria and Toll-like Receptor (TLR) Signaling

(2015) Ming Shi et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Redistribution, Hyperproliferation, Activation of Natural Killer Cells and CD8 T Cells, and Cytokine Production During First-in-Human Clinical Trial of Recombinant Human Interleukin-15 in Patients With Cancer

(2015) Kevin C. Conlon et al.   JOURNAL OF CLINICAL ONCOLOGY

Liposomes loaded with a STING pathway ligand, cyclic di-GMP, enhance cancer immunotherapy against metastatic melanoma

(2015) Takashi Nakamura et al.   JOURNAL OF CONTROLLED RELEASE

Hypoxia induced HMGB1 and mitochondrial DNA interactions mediate tumor growth in hepatocellular carcinoma through Toll-like receptor 9

(2015) Yao Liu et al.   JOURNAL OF HEPATOLOGY

CD47 blockade triggers T cell–mediated destruction of immunogenic tumors

(2015) Xiaojuan Liu et al.   NATURE MEDICINE

Poly(I:C) as cancer vaccine adjuvant: Knocking on the door of medical breakthroughs

(2015) Rachid Ammi et al.   PHARMACOLOGY & THERAPEUTICS

STING activation of tumor endothelial cells initiates spontaneous and therapeutic antitumor immunity

(2015) Olivier Demaria et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

STING agonist formulated cancer vaccines can cure established tumors resistant to PD-1 blockade

(2015) Juan Fu et al.   Science Translational Medicine

Enhancing Cancer Immunotherapy Via Activation of Innate Immunity

(2015) Jacob L. Goldberg et al.   SEMINARS IN ONCOLOGY

Direct Activation of STING in the Tumor Microenvironment Leads to Potent and Systemic Tumor Regression and Immunity

(2015) Leticia Corrales et al.   Cell Reports

Impact of 2-, 4- and 9-valent HPV vaccines on morbidity and mortality from cervical cancer

(2015) Rebecca Luckett et al.   Human Vaccines & Immunotherapeutics

TLR activation and ionizing radiation induce strong immune responses against multiple tumor entities

(2015) Sebastian Schölch et al.   OncoImmunology

Splenectomy inhibits non-small cell lung cancer growth by modulating anti-tumor adaptive and innate immune response

(2015) Liran Levy et al.   OncoImmunology

IFNγ producing CD8+T cells modified to resist major immune checkpoints induce regression of MHC class I-deficient melanomas

(2015) Michel Buferne et al.   OncoImmunology

Pancreatic Cancer-Specific Cell Death Induced In Vivo by Cytoplasmic-Delivered Polyinosine-Polycytidylic Acid

(2014) P. Bhoopathi et al.   CANCER RESEARCH

SA-4-1BBL and Monophosphoryl Lipid A Constitute an Efficacious Combination Adjuvant for Cancer Vaccines

(2014) A. K. Srivastava et al.   CANCER RESEARCH

Apoptotic Caspases Suppress mtDNA-Induced STING-Mediated Type I IFN Production

(2014) Michael J. White et al.   CELL

The IL-2 cytokine family in cancer immunotherapy

(2014) Geok Choo Sim et al.   CYTOKINE & GROWTH FACTOR REVIEWS

STING-Dependent Cytosolic DNA Sensing Mediates Innate Immune Recognition of Immunogenic Tumors

(2014) Seng-Ryong Woo et al.   IMMUNITY

STING-Dependent Cytosolic DNA Sensing Promotes Radiation-Induced Type I Interferon-Dependent Antitumor Immunity in Immunogenic Tumors

(2014) Liufu Deng et al.   IMMUNITY

IL-2: The First Effective Immunotherapy for Human Cancer

(2014) S. A. Rosenberg   JOURNAL OF IMMUNOLOGY

A Novel Mitochondrial MAVS/Caspase-8 Platform Links RNA Virus-Induced Innate Antiviral Signaling to Bax/Bak-Independent Apoptosis

(2014) S. El Maadidi et al.   JOURNAL OF IMMUNOLOGY

Cytosolic-DNA-Mediated, STING-Dependent Proinflammatory Gene Induction Necessitates Canonical NF- B Activation through TBK1

(2014) T. Abe et al.   JOURNAL OF VIROLOGY

Anti-programmed-death-receptor-1 treatment with pembrolizumab in ipilimumab-refractory advanced melanoma: a randomised dose-comparison cohort of a phase 1 trial

(2014) Caroline Robert et al.   LANCET

Structural basis for ubiquitin-mediated antiviral signal activation by RIG-I

(2014) Alys Peisley et al.   NATURE

PD-1 blockade induces responses by inhibiting adaptive immune resistance

(2014) Paul C. Tumeh et al.   NATURE

MAP1S Controls Breast Cancer Cell TLR5 Signaling Pathway and Promotes TLR5 Signaling-based Tumor Suppression

(2014) Ming Shi et al.   PLoS One

DMXAA Causes Tumor Site-Specific Vascular Disruption in Murine Non-Small Cell Lung Cancer, and like the Endogenous Non-Canonical Cyclic Dinucleotide STING Agonist, 2′3′-cGAMP, Induces M2 Macrophage Repolarization

(2014) Charlene M. Downey et al.   PLoS One

The Laboratory of Genetics and Physiology 2: Emerging Insights into the Controversial Functions of This RIG-I-Like Receptor

(2014) Zixiang Zhu et al.   Biomed Research International

STING Contributes to Antiglioma Immunity via Triggering Type I IFN Signals in the Tumor Microenvironment

(2014) T. Ohkuri et al.   Cancer Immunology Research

Toll-Like Receptors and Prostate Cancer

(2014) Shu Zhao et al.   Frontiers in Immunology

Using macrophage activation to augment immunotherapy of established tumours

(2013) Z G Fridlender et al.   BRITISH JOURNAL OF CANCER

Therapeutic Efficacy of Bifunctional siRNA Combining TGF- 1 Silencing with RIG-I Activation in Pancreatic Cancer

(2013) J. Ellermeier et al.   CANCER RESEARCH

Structure-Function Analysis of STING Activation by c[G(2′,5′)pA(3′,5′)p] and Targeting by Antiviral DMXAA

(2013) Pu Gao et al.   CELL

Host Restriction Factor SAMHD1 Limits Human T Cell Leukemia Virus Type 1 Infection of Monocytes via STING-Mediated Apoptosis

(2013) Alexandre Sze et al.   Cell Host & Microbe

Nucleic acid driven sterile inflammation

(2013) Andrea Ablasser et al.   CLINICAL IMMUNOLOGY

Master sensors of pathogenic RNA – RIG-I like receptors

(2013) Martin Schlee   IMMUNOBIOLOGY

Targeting Uptake Receptors on Human Plasmacytoid Dendritic Cells Triggers Antigen Cross-Presentation and Robust Type I IFN Secretion

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

Cutting Edge: DNA Sensing via the STING Adaptor in Myeloid Dendritic Cells Induces Potent Tolerogenic Responses

(2013) L. Huang et al.   JOURNAL OF IMMUNOLOGY

Mouse, but not Human STING, Binds and Signals in Response to the Vascular Disrupting Agent 5,6-Dimethylxanthenone-4-Acetic Acid

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

Pattern Recognition Theory and the Launch of Modern Innate Immunity

(2013) R. Medzhitov   JOURNAL OF IMMUNOLOGY

MAVS Regulates Apoptotic Cell Death by Decreasing K48-Linked Ubiquitination of Voltage-Dependent Anion Channel 1

(2013) Kai Guan et al.   MOLECULAR AND CELLULAR BIOLOGY

Cyclic GMP-AMP Containing Mixed Phosphodiester Linkages Is An Endogenous High-Affinity Ligand for STING

(2013) Xu Zhang et al.   MOLECULAR CELL

cGAS produces a 2′-5′-linked cyclic dinucleotide second messenger that activates STING

(2013) Andrea Ablasser et al.   NATURE

Detecting and targeting tumor relapse by its resistance to innate effectors at early recurrence

(2013) Timothy Kottke et al.   NATURE MEDICINE

Immunosuppressive networks and checkpoints controlling antitumor immunity and their blockade in the development of cancer immunotherapeutics and vaccines

(2013) A Q Butt et al.   ONCOGENE

Central role of liver in anticancer and radioprotective activities of Toll-like receptor 5 agonist

(2013) L. G. Burdelya et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

STING-IRF3 pathway links endoplasmic reticulum stress with hepatocyte apoptosis in early alcoholic liver disease

(2013) J. Petrasek et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

DNA damage sensor MRE11 recognizes cytosolic double-stranded DNA and induces type I interferon by regulating STING trafficking

(2013) T. Kondo et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Prolonged subcutaneous administration of 852A, a novel systemic toll-like receptor 7 agonist, to activate innate immune responses in patients with advanced hematologic malignancies

(2012) Brenda J. Weigel et al.   AMERICAN JOURNAL OF HEMATOLOGY

STAT3-Driven Upregulation of TLR2 Promotes Gastric Tumorigenesis Independent of Tumor Inflammation

(2012) Hazel Tye et al.   CANCER CELL

Enhancement of the anti-melanoma response of Hu14.18K322A by αCD40 + CpG

(2012) Kory L. Alderson et al.   CANCER IMMUNOLOGY IMMUNOTHERAPY

The HumanTLRInnate Immune Gene Family Is Differentially Influenced by DNA Stress andp53Status in Cancer Cells

(2012) Maria Shatz et al.   CANCER RESEARCH

Extracts of Larix Leptolepis effectively augments the generation of tumor antigen-specific cytotoxic T lymphocytes via activation of dendritic cells in TLR-2 and TLR-4-dependent manner

(2012) Shin-ichi Koizumi et al.   CELLULAR IMMUNOLOGY

Topical TLR7 Agonist Imiquimod Can Induce Immune-Mediated Rejection of Skin Metastases in Patients with Breast Cancer

(2012) S. Adams et al.   CLINICAL CANCER RESEARCH

Synergy of Topical Toll-like Receptor 7 Agonist with Radiation and Low-Dose Cyclophosphamide in a Mouse Model of Cutaneous Breast Cancer

(2012) M. Z. Dewan et al.   CLINICAL CANCER RESEARCH

TRAIL and Noxa Are Selectively Upregulated in Prostate Cancer Cells Downstream of the RIG-I/MAVS Signaling Pathway by Nonreplicating Sendai Virus Particles

(2012) T. Matsushima-Miyagi et al.   CLINICAL CANCER RESEARCH

Molecular Pathways: Toll-like Receptors in the Tumor Microenvironment--Poor Prognosis or New Therapeutic Opportunity

(2012) L. A. Ridnour et al.   CLINICAL CANCER RESEARCH

Ubiquitin-Induced Oligomerization of the RNA Sensors RIG-I and MDA5 Activates Antiviral Innate Immune Response

(2012) Xiaomo Jiang et al.   IMMUNITY

TRAIL+ Human Plasmacytoid Dendritic Cells Kill Tumor Cells In Vitro: Mechanisms of Imiquimod- and IFN- -Mediated Antitumor Reactivity

(2012) M. L. Kalb et al.   JOURNAL OF IMMUNOLOGY

Intratumoral Delivery of Low Doses of Anti-CD40 mAb Combined With Monophosphoryl Lipid A Induces Local and Systemic Antitumor Effects in Immunocompetent and T Cell-Deficient Mice

(2012) Tyler J. Van De Voort et al.   JOURNAL OF IMMUNOTHERAPY

A structure-based model of RIG-I activation

(2012) D. Kolakofsky et al.   RNA

Cyclic GMP-AMP Synthase Is a Cytosolic DNA Sensor That Activates the Type I Interferon Pathway

(2012) L. Sun et al.   SCIENCE

DNA-PK is a DNA sensor for IRF-3-dependent innate immunity

(2012) Brian J Ferguson et al.   eLife

Trial Watch

(2012) Lorenzo Galluzzi et al.   OncoImmunology

HMGB1 and Microparticles as Mediators of the Immune Response to Cell Death

(2011) David S. Pisetsky et al.   ANTIOXIDANTS & REDOX SIGNALING

Anticancer function of polyinosinic-polycytidylic acid

(2011) Yu-sheng Cheng et al.   CANCER BIOLOGY & THERAPY

Activation of Toll-like Receptor 5 on Breast Cancer Cells by Flagellin Suppresses Cell Proliferation and Tumor Growth

(2011) Z. Cai et al.   CANCER RESEARCH

Toll-Like Receptor Transcriptome in the HPV-Positive Cervical Cancer Microenvironment

(2011) Correne A. DeCarlo et al.   Clinical & Developmental Immunology

Immunogenic cell death of human ovarian cancer cells induced by cytosolic poly(I:C) leads to myeloid cell maturation and activates NK cells

(2011) Kirsten Kübler et al.   EUROPEAN JOURNAL OF IMMUNOLOGY

Cutting Edge: Ku70 Is a Novel Cytosolic DNA Sensor That Induces Type III Rather Than Type I IFN

(2011) X. Zhang et al.   JOURNAL OF IMMUNOLOGY

MPYS Is Required for IFN Response Factor 3 Activation and Type I IFN Production in the Response of Cultured Phagocytes to Bacterial Second Messengers Cyclic-di-AMP and Cyclic-di-GMP

(2011) L. Jin et al.   JOURNAL OF IMMUNOLOGY

Apoptosis Induced by Mammalian Reovirus Is Beta Interferon (IFN) Independent and Enhanced by IFN Regulatory Factor 3- and NF- B-Dependent Expression of Noxa

(2011) J. J. Knowlton et al.   JOURNAL OF VIROLOGY

STING is a direct innate immune sensor of cyclic di-GMP

(2011) Dara L. Burdette et al.   NATURE

The helicase DDX41 senses intracellular DNA mediated by the adaptor STING in dendritic cells

(2011) Zhiqiang Zhang et al.   NATURE IMMUNOLOGY

Intracerebral administration of CpG oligonucleotide for patients with recurrent glioblastoma: a phase II study

(2011) A. Carpentier et al.   NEURO-ONCOLOGY

Induction of Noxa-Mediated Apoptosis by Modified Vaccinia Virus Ankara Depends on Viral Recognition by Cytosolic Helicases, Leading to IRF-3/IFN-β-Dependent Induction of Pro-Apoptotic Noxa

(2011) Pedro Eitz Ferrer et al.   PLoS Pathogens

The M1 form of tumor-associated macrophages in non-small cell lung cancer is positively associated with survival time

(2010) Junliang Ma et al.   BMC CANCER

Viral apoptosis is induced by IRF-3-mediated activation of Bax

(2010) Saurabh Chattopadhyay et al.   EMBO JOURNAL

Inhibiting the inhibitors: evaluating agents targeting cancer immunosuppression

(2010) Theresa L Whiteside   EXPERT OPINION ON BIOLOGICAL THERAPY

Immunogene therapy using immunomodulating HVJ-E vector augments anti-tumor effects in murine malignant glioma

(2010) Masahide Matsuda et al.   JOURNAL OF NEURO-ONCOLOGY

The cytosolic nucleic acid sensor LRRFIP1 mediates the production of type I interferon via a β-catenin-dependent pathway

(2010) Pengyuan Yang et al.   NATURE IMMUNOLOGY

IFI16 is an innate immune sensor for intracellular DNA

(2010) Leonie Unterholzner et al.   NATURE IMMUNOLOGY

Aspartate-glutamate-alanine-histidine box motif (DEAH)/RNA helicase A helicases sense microbial DNA in human plasmacytoid dendritic cells

(2010) T. Kim et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

RNA Polymerase III Detects Cytosolic DNA and Induces Type I Interferons through the RIG-I Pathway

(2009) Yu-Hsin Chiu et al.   CELL

Proapoptotic signaling induced by RIG-I and MDA-5 results in type I interferon–independent apoptosis in human melanoma cells

(2009) Robert Besch et al.   JOURNAL OF CLINICAL INVESTIGATION

The Interferon Stimulator Mitochondrial Antiviral Signaling Protein Facilitates Cell Death by Disrupting the Mitochondrial Membrane Potential and by Activating Caspases

(2009) C.-Y. Yu et al.   JOURNAL OF VIROLOGY

AIM2 recognizes cytosolic dsDNA and forms a caspase-1-activating inflammasome with ASC

(2009) Veit Hornung et al.   NATURE

Inflaming metastasis

(2009) Alberto Mantovani   NATURE

STING regulates intracellular DNA-mediated, type I interferon-dependent innate immunity

(2009) Hiroki Ishikawa et al.   NATURE

Carcinoma-produced factors activate myeloid cells through TLR2 to stimulate metastasis

(2009) Sunhwa Kim et al.   NATURE

An orthogonal proteomic-genomic screen identifies AIM2 as a cytoplasmic DNA sensor for the inflammasome

(2009) Tilmann Bürckstümmer et al.   NATURE IMMUNOLOGY

MAVS-Mediated Apoptosis and Its Inhibition by Viral Proteins

(2009) Yu Lei et al.   PLoS One

On the Origin of The Immune System

(2009) J. Travis   SCIENCE

The Adaptor Protein MITA Links Virus-Sensing Receptors to IRF3 Transcription Factor Activation

(2008) Bo Zhong et al.   IMMUNITY

STING is an endoplasmic reticulum adaptor that facilitates innate immune signalling

(2008) Hiroki Ishikawa et al.   NATURE

5′-triphosphate-siRNA: turning gene silencing and Rig-I activation against melanoma

(2008) Hendrik Poeck et al.   NATURE MEDICINE

Cancers take their Toll—the function and regulation of Toll-like receptors in cancer cells

(2008) R Chen et al.   ONCOGENE

History of Bacillus Calmette-Guerin and Bladder Cancer: An Immunotherapy Success Story

(2007) Harry W. Herr et al.   JOURNAL OF UROLOGY

Therapeutics targeting tumor immune escape: Towards the development of new generation anticancer vaccines

(2007) Simone Mocellin et al.   MEDICINAL RESEARCH REVIEWS