Roles of the RANKL–RANK axis in antitumour immunity — implications for therapy

Emerging Concepts for Immune Checkpoint Blockade-Based Combination Therapies

(2018) Roberta Zappasodi et al.   CANCER CELL

The anti-tumor effect of RANKL inhibition in malignant solid tumors – A systematic review

(2018) A.F. de Groot et al.   CANCER TREATMENT REVIEWS

Phase I Trial of M7824 (MSB0011359C), a Bifunctional Fusion Protein Targeting PD-L1 and TGFβ, in Advanced Solid Tumors

(2018) Julius Strauss et al.   CLINICAL CANCER RESEARCH

The Tumor Necrosis Factor Superfamily Member RANKL Suppresses Effector Cytokine Production in Group 3 Innate Lymphoid Cells

(2018) Jennifer K. Bando et al.   IMMUNITY

RANKL Signaling Sustains Primary Tumor Growth in Genetically Engineered Mouse Models of Lung Adenocarcinoma

(2018) Julien Faget et al.   Journal of Thoracic Oncology

Pembrolizumab plus Chemotherapy in Metastatic Non–Small-Cell Lung Cancer

(2018) Leena Gandhi et al.   NEW ENGLAND JOURNAL OF MEDICINE

Characteristics of Real‐World Metastatic Non‐Small Cell Lung Cancer Patients Treated with Nivolumab and Pembrolizumab During the Year Following Approval

(2018) Sean Khozin et al.   ONCOLOGIST

RANKL blockade improves efficacy of PD1-PD-L1 blockade or dual PD1-PD-L1 and CTLA4 blockade in mouse models of cancer

(2018) Elizabeth Ahern et al.   OncoImmunology

An observational study of concomitant immunotherapies and denosumab in patients with advanced melanoma or lung cancer

(2018) Alexander Liede et al.   OncoImmunology

TGFβ attenuates tumour response to PD-L1 blockade by contributing to exclusion of T cells

(2018) Sanjeev Mariathasan et al.   NATURE

Denosumab in advanced/unresectable giant-cell tumour of bone (GCTB): For how long?

(2017) E. Palmerini et al.   EUROPEAN JOURNAL OF CANCER

Real-world treatment outcomes in patients with metastatic Merkel cell carcinoma treated with chemotherapy in the USA

(2017) C Lance Cowey et al.   Future Oncology

RANK rewires energy homeostasis in lung cancer cells and drives primary lung cancer

(2017) Shuan Rao et al.   GENES & DEVELOPMENT

Reactive Neutrophil Responses Dependent on the Receptor Tyrosine Kinase c-MET Limit Cancer Immunotherapy

(2017) Nicole Glodde et al.   IMMUNITY

Estrogens and androgens inhibit association of RANKL with the pre-osteoblast membrane through post-translational mechanisms

(2017) Anthony Martin et al.   JOURNAL OF CELLULAR PHYSIOLOGY

ILC2-modulated T cell–to-MDSC balance is associated with bladder cancer recurrence

(2017) Mathieu F. Chevalier et al.   JOURNAL OF CLINICAL INVESTIGATION

Osteoclast regulation of osteoblasts via RANK-RANKL reverse signal transduction in vitro

(2017) Shiqian Zhang et al.   Molecular Medicine Reports

Overall Survival with Combined Nivolumab and Ipilimumab in Advanced Melanoma

(2017) Jedd D. Wolchok et al.   NEW ENGLAND JOURNAL OF MEDICINE

First-Line Nivolumab in Stage IV or Recurrent Non–Small-Cell Lung Cancer

(2017) David P. Carbone et al.   NEW ENGLAND JOURNAL OF MEDICINE

Tumour-derived PGD2 and NKp30-B7H6 engagement drives an immunosuppressive ILC2-MDSC axis

(2017) Sara Trabanelli et al.   Nature Communications

Distribution of RANK and RANK Ligand in Normal Human Tissues as Determined by an Optimized Immunohistochemical Method

(2017) Clive R. Taylor et al.   APPLIED IMMUNOHISTOCHEMISTRY & MOLECULAR MORPHOLOGY

10 years of denosumab treatment in postmenopausal women with osteoporosis: results from the phase 3 randomised FREEDOM trial and open-label extension

(2017) Henry G Bone et al.   Lancet Diabetes & Endocrinology

Estrogen Regulates Bone Turnover by Targeting RANKL Expression in Bone Lining Cells

(2017) Carmen Streicher et al.   Scientific Reports

RANK-RANKL signalling in cancer

(2016) N. Renema et al.   BIOSCIENCE REPORTS

Osteoclasts promote immune suppressive microenvironment in multiple myeloma: therapeutic implication

(2016) G. An et al.   BLOOD

Can we prevent BRCA1-associated breast cancer by RANKL inhibition?

(2016) Joanne Kotsopoulos et al.   BREAST CANCER RESEARCH AND TREATMENT

RANK Signaling Blockade Reduces Breast Cancer Recurrence by Inducing Tumor Cell Differentiation

(2016) Guillermo Yoldi et al.   CANCER RESEARCH

RANKL/RANK control Brca1 mutation-driven mammary tumors

(2016) Verena Sigl et al.   CELL RESEARCH

Expansion and Activation of CD103 + Dendritic Cell Progenitors at the Tumor Site Enhances Tumor Responses to Therapeutic PD-L1 and BRAF Inhibition

(2016) Hélène Salmon et al.   IMMUNITY

Association of Pembrolizumab With Tumor Response and Survival Among Patients With Advanced Melanoma

(2016) Antoni Ribas et al.   JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION

Combination Anti-CTLA-4 and Anti-RANKL in Metastatic Melanoma

(2016) Mark J. Smyth et al.   JOURNAL OF CLINICAL ONCOLOGY

Nivolumab Monotherapy for First-Line Treatment of Advanced Non–Small-Cell Lung Cancer

(2016) Scott Gettinger et al.   JOURNAL OF CLINICAL ONCOLOGY

Overcoming resistance to checkpoint blockade therapy by targeting PI3Kγ in myeloid cells

(2016) Olivier De Henau et al.   NATURE

LGR4 is a receptor for RANKL and negatively regulates osteoclast differentiation and bone resorption

(2016) Jian Luo et al.   NATURE MEDICINE

RANK ligand as a potential target for breast cancer prevention in BRCA1-mutation carriers

(2016) Emma Nolan et al.   NATURE MEDICINE

Pembrolizumab versus Chemotherapy for PD-L1–Positive Non–Small-Cell Lung Cancer

(2016) Martin Reck et al.   NEW ENGLAND JOURNAL OF MEDICINE

AB0908 Findings From Denosumab (Prolia®) Postmarketing Safety Surveillance for Serious Infections: Table 1.

(2015) W. Golden et al.   ANNALS OF THE RHEUMATIC DISEASES

Estrogens antagonize RUNX2-mediated osteoblast-driven osteoclastogenesis through regulating RANKL membrane association

(2015) Anthony Martin et al.   BONE

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

(2015) Padmanee Sharma et al.   CELL

Tumor-Infiltrating Dendritic Cells in Cancer Pathogenesis

(2015) Jo Marie Tran Janco et al.   JOURNAL OF IMMUNOLOGY

Receptor Activator of NF-κB Ligand Promotes the Production of CCL17 from RANK+ M2 Macrophages

(2015) Taku Fujimura et al.   JOURNAL OF INVESTIGATIVE DERMATOLOGY

The Possible Interaction between Receptor Activator of Nuclear Factor Kappa-B Ligand Expressed by Extramammary Paget Cells and its Ligand on Dermal Macrophages

(2015) Yumi Kambayashi et al.   JOURNAL OF INVESTIGATIVE DERMATOLOGY

Adjuvant denosumab in breast cancer (ABCSG-18): a multicentre, randomised, double-blind, placebo-controlled trial

(2015) Michael Gnant et al.   LANCET

Combination cancer immunotherapies tailored to the tumour microenvironment

(2015) Mark J. Smyth et al.   Nature Reviews Clinical Oncology

Nivolumab in Previously Untreated Melanoma without BRAF Mutation

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

Nivolumab and Ipilimumab versus Ipilimumab in Untreated Melanoma

(2015) Michael A. Postow 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

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

(2015) Hossein Borghaei 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

NCR+ILC3 concentrate in human lung cancer and associate with intratumoral lymphoid structures

(2015) Paolo Carrega et al.   Nature Communications

Risk of Hospitalized Infection Among Rheumatoid Arthritis Patients Concurrently Treated With a Biologic Agent and Denosumab

(2015) Jeffrey R. Curtis et al.   Arthritis & Rheumatology

Cervical (pre)neoplastic microenvironment promotes the emergence of tolerogenic dendritic cells via RANKL secretion

(2015) Stéphanie A Demoulin et al.   OncoImmunology

Rapid complete response of metastatic melanoma in a patient undergoing ipilimumab immunotherapy in the setting of active ulcerative colitis

(2015) A Doran Bostwick et al.   Journal for ImmunoTherapy of Cancer

The immune system, bone and RANKL

(2014) Matteo M. Guerrini et al.   ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS

Human Osteoclasts Are Inducible Immunosuppressive Cells in Response to T cell-Derived IFN-γ and CD40 Ligand In Vitro

(2014) Haiyan Li et al.   JOURNAL OF BONE AND MINERAL RESEARCH

B7-H1–expressing antigen-presenting cells mediate polarization of protumorigenic Th22 subsets

(2014) Dong-Ming Kuang et al.   JOURNAL OF CLINICAL INVESTIGATION

Enhancement of an anti-tumor immune response by transient blockade of central T cell tolerance

(2014) Imran S. Khan et al.   JOURNAL OF EXPERIMENTAL MEDICINE

Organizer-Like Reticular Stromal Cell Layer Common to Adult Secondary Lymphoid Organs

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

Epidermal Receptor Activator of NF- B Ligand Controls Langerhans Cells Numbers and Proliferation

(2014) J.-B. O. Barbaroux et al.   JOURNAL OF IMMUNOLOGY

Clinical development success rates for investigational drugs

(2014) Michael Hay et al.   NATURE BIOTECHNOLOGY

Bisphosphonate-osteoclasts: Changes in osteoclast morphology and function induced by antiresorptive nitrogen-containing bisphosphonate treatment in osteoporosis patients

(2013) Björn Jobke et al.   BONE

RORγt+ Innate Lymphoid Cells Acquire a Proinflammatory Program upon Engagement of the Activating Receptor NKp44

(2013) Timor Glatzer et al.   IMMUNITY

Oncology Meets Immunology: The Cancer-Immunity Cycle

(2013) Daniel S. Chen et al.   IMMUNITY

Immunology and bone

(2013) L. Danks et al.   JOURNAL OF BIOCHEMISTRY

Innate lymphoid cells sustain colon cancer through production of interleukin-22 in a mouse model

(2013) Stefanie Kirchberger et al.   JOURNAL OF EXPERIMENTAL MEDICINE

Safety and efficacy of denosumab for adults and skeletally mature adolescents with giant cell tumour of bone: interim analysis of an open-label, parallel-group, phase 2 study

(2013) Sant Chawla et al.   LANCET ONCOLOGY

Aire-Dependent Thymic Development of Tumor-Associated Regulatory T Cells

(2013) S. Malchow et al.   SCIENCE

Progesterone/RANKL Is a Major Regulatory Axis in the Human Breast

(2013) T. Tanos et al.   Science Translational Medicine

RANK Induces Epithelial-Mesenchymal Transition and Stemness in Human Mammary Epithelial Cells and Promotes Tumorigenesis and Metastasis

(2012) M. Palafox et al.   CANCER RESEARCH

Myeloid-Derived Suppressor Cells Function as Novel Osteoclast Progenitors Enhancing Bone Loss in Breast Cancer

(2012) A. Sawant et al.   CANCER RESEARCH

RANKL Expression, Function, and Therapeutic Targeting in Multiple Myeloma and Chronic Lymphocytic Leukemia

(2012) B. J. Schmiedel et al.   CANCER RESEARCH

Denosumab Dose Selection for Patients with Bone Metastases from Solid Tumors

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

Denosumab Induces Tumor Reduction and Bone Formation in Patients with Giant-Cell Tumor of Bone

(2012) D. G. Branstetter et al.   CLINICAL CANCER RESEARCH

Superiority of denosumab to zoledronic acid for prevention of skeletal-related events: A combined analysis of 3 pivotal, randomised, phase 3 trials

(2012) Allan Lipton et al.   EUROPEAN JOURNAL OF CANCER

Rank Signaling Links the Development of Invariant γδ T Cell Progenitors and Aire+ Medullary Epithelium

(2012) Natalie A. Roberts et al.   IMMUNITY

Expression pattern changes and function of RANKL during mouse lymph node microarchitecture development

(2012) Machiko Sugiyama et al.   INTERNATIONAL IMMUNOLOGY

Receptor Activator for NF- B Ligand in Acute Myeloid Leukemia: Expression, Function, and Modulation of NK Cell Immunosurveillance

(2012) B. J. Schmiedel et al.   JOURNAL OF IMMUNOLOGY

Crystal Structure of Human RANKL Complexed with Its Decoy Receptor Osteoprotegerin

(2012) X. Luan et al.   JOURNAL OF IMMUNOLOGY

Overall Survival Improvement in Patients with Lung Cancer and Bone Metastases Treated with Denosumab Versus Zoledronic Acid: Subgroup Analysis from a Randomized Phase 3 Study

(2012) Giorgio Vittorio Scagliotti et al.   Journal of Thoracic Oncology

Bench to bedside: elucidation of the OPG–RANK–RANKL pathway and the development of denosumab

(2012) David L. Lacey et al.   NATURE REVIEWS DRUG DISCOVERY

Diagnosing the decline in pharmaceutical R&D efficiency

(2012) Jack W. Scannell et al.   NATURE REVIEWS DRUG DISCOVERY

The Immune Response to Melanoma Is Limited by Thymic Selection of Self-Antigens

(2012) Ulrike Träger et al.   PLoS One

RANKL Employs Distinct Binding Modes to Engage RANK and the Osteoprotegerin Decoy Receptor

(2012) Christopher A. Nelson et al.   STRUCTURE

Mesenchymal cell differentiation during lymph node organogenesis

(2012) Andrea Brendolan et al.   Frontiers in Immunology

Myeloid-derived suppressor cells expand during breast cancer progression and promote tumor-induced bone destruction

(2012) Sabrina Danilin et al.   OncoImmunology

Denosumab, a fully human RANKL antibody, reduced bone turnover markers and increased trabecular and cortical bone mass, density, and strength in ovariectomized cynomolgus monkeys

(2011) Michael S. Ominsky et al.   BONE

Molecular Pathways: Osteoclast-Dependent and Osteoclast-Independent Roles of the RANKL/RANK/OPG Pathway in Tumorigenesis and Metastasis

(2011) W. C. Dougall   CLINICAL CANCER RESEARCH

Control of central and peripheral tolerance by Aire

(2011) Todd C. Metzger et al.   IMMUNOLOGICAL REVIEWS

Randomized, Double-Blind Study of Denosumab Versus Zoledronic Acid in the Treatment of Bone Metastases in Patients With Advanced Cancer (Excluding Breast and Prostate Cancer) or Multiple Myeloma

(2011) David H. Henry et al.   JOURNAL OF CLINICAL ONCOLOGY

RANKL Induces Organized Lymph Node Growth by Stromal Cell Proliferation

(2011) E. Hess et al.   JOURNAL OF IMMUNOLOGY

Denosumab versus zoledronic acid for treatment of bone metastases in men with castration-resistant prostate cancer: a randomised, double-blind study

(2011) Karim Fizazi et al.   LANCET

Denosumab and bone-metastasis-free survival in men with castration-resistant prostate cancer: results of a phase 3, randomised, placebo-controlled trial

(2011) Matthew R Smith et al.   LANCET

Tumour-infiltrating regulatory T cells stimulate mammary cancer metastasis through RANKL–RANK signalling

(2011) Wei Tan et al.   NATURE

Infections in postmenopausal women with osteoporosis treated with denosumab or placebo: coincidence or causal association?

(2011) N. B. Watts et al.   OSTEOPOROSIS INTERNATIONAL

Clinical Efficacy and Safety of Denosumab in Postmenopausal Women with Low Bone Mineral Density and Osteoporosis: A Meta-Analysis

(2011) Camilla von Keyserlingk et al.   SEMINARS IN ARTHRITIS AND RHEUMATISM

Cross talk between the bone and immune systems: osteoclasts function as antigen-presenting cells and activate CD4+ and CD8+ T cells

(2010) H. Li et al.   BLOOD

Expression pattern of receptor activator of NFκB (RANK) in a series of primary solid tumors and related bone metastases

(2010) Daniele Santini et al.   JOURNAL OF CELLULAR PHYSIOLOGY

Denosumab Compared With Zoledronic Acid for the Treatment of Bone Metastases in Patients With Advanced Breast Cancer: A Randomized, Double-Blind Study

(2010) Alison T. Stopeck et al.   JOURNAL OF CLINICAL ONCOLOGY

RANK ligand mediates progestin-induced mammary epithelial proliferation and carcinogenesis

(2010) Eva Gonzalez-Suarez et al.   NATURE

Control of mammary stem cell function by steroid hormone signalling

(2010) Marie-Liesse Asselin-Labat et al.   NATURE

Osteoclast differentiation factor RANKL controls development of progestin-driven mammary cancer

(2010) Daniel Schramek et al.   NATURE

Improved Survival with Ipilimumab in Patients with Metastatic Melanoma

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

Giant cell tumour of bone

(2009) David M Thomas et al.   CURRENT OPINION IN ONCOLOGY

Randomized Phase II Trial of Denosumab in Patients With Bone Metastases From Prostate Cancer, Breast Cancer, or Other Neoplasms After Intravenous Bisphosphonates

(2009) Karim Fizazi et al.   JOURNAL OF CLINICAL ONCOLOGY

Cross-Presentation by Osteoclasts Induces FoxP3 in CD8+ T Cells

(2009) J. R. Kiesel et al.   JOURNAL OF IMMUNOLOGY

RANK-RANKL Signaling Pathway Is Critically Involved in the Function of CD4 + CD25 + Regulatory T Cells in Chronic Colitis

(2009) Teruji Totsuka et al.   JOURNAL OF IMMUNOLOGY

Increased RANKL expression is related to tumour migration and metastasis of renal cell carcinomas

(2009) Shuji Mikami et al.   JOURNAL OF PATHOLOGY

Denosumab for Prevention of Fractures in Postmenopausal Women with Osteoporosis

(2009) Steven R. Cummings et al.   NEW ENGLAND JOURNAL OF MEDICINE

Development of Secondary Lymphoid Organs

(2008) Troy D. Randall et al.   Annual Review of Immunology

Functions of RANKL/RANK/OPG in bone modeling and remodeling

(2008) Brendan F. Boyce et al.   ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS

Bone markers and their prognostic value in metastatic bone disease: Clinical evidence and future directions

(2008) Robert Coleman et al.   CANCER TREATMENT REVIEWS

Epithelial to mesenchymal transition (EMT) in human prostate cancer: lessons learned from ARCaP model

(2008) Haiyen E. Zhau et al.   CLINICAL & EXPERIMENTAL METASTASIS

The Cytokine RANKL Produced by Positively Selected Thymocytes Fosters Medullary Thymic Epithelial Cells that Express Autoimmune Regulator

(2008) Yu Hikosaka et al.   IMMUNITY

The Tumor Necrosis Factor Family Receptors RANK and CD40 Cooperatively Establish the Thymic Medullary Microenvironment and Self-Tolerance

(2008) Taishin Akiyama et al.   IMMUNITY