Therapeutic targeting of TGF-β in cancer: hacking a master switch of immune suppression

Oncolytic adenovirus targeting TGF-β enhances anti-tumor responses of mesothelin-targeted chimeric antigen receptor T cell therapy against breast cancer

(2020) Yuxiang Li et al.   CELLULAR IMMUNOLOGY

Selection of the Recommended Phase 2 Dose for Bintrafusp Alfa, a Bifunctional Fusion Protein Targeting TGF‐β and PD‐L1

(2020) Yulia Vugmeyster et al.   CLINICAL PHARMACOLOGY & THERAPEUTICS

Thrombin contributes to cancer immune evasion via proteolysis of platelet-bound GARP to activate LTGF-β

(2020) Alessandra Metelli et al.   Science Translational Medicine

A Potent Pan-TGFβ Neutralizing Monoclonal Antibody Elicits Cardiovascular Toxicity in Mice and Cynomolgus Monkeys

(2020) Mayur S Mitra et al.   TOXICOLOGICAL SCIENCES

Safety and Tolerability of Bintrafusp Alfa, a Bifunctional Fusion Protein Targeting TGFβ and PD-L1, in Asian Patients with Pretreated Recurrent or Refractory Gastric Cancer

(2020) Yoon-Koo Kang et al.   CLINICAL CANCER RESEARCH

Bintrafusp Alfa, a Bifunctional Fusion Protein Targeting TGF-β and PD-L1, in Second-Line Treatment of Patients With NSCLC: Results From an Expansion Cohort of a Phase 1 Trial

(2020) Luis Paz-Ares et al.   Journal of Thoracic Oncology

Neoadjuvant immunotherapy leads to pathological responses in MMR-proficient and MMR-deficient early-stage colon cancers

(2020) Myriam Chalabi et al.   NATURE MEDICINE

Phase I Study of the Bifunctional Fusion Protein Bintrafusp Alfa in Asian Patients with Advanced Solid Tumors, Including a Hepatocellular Carcinoma Safety‐Assessment Cohort

(2020) Toshihiko Doi et al.   ONCOLOGIST

Selective inhibition of TGFβ1 activation overcomes primary resistance to checkpoint blockade therapy by altering tumor immune landscape

(2020) Constance J. Martin et al.   Science Translational Medicine

Immunotherapeutic Potential of TGF-β Inhibition and Oncolytic Viruses

(2020) Christianne Groeneveldt et al.   TRENDS IN IMMUNOLOGY

TGFβ suppresses CD8+ T cell expression of CXCR3 and tumor trafficking

(2020) Andrew J. Gunderson et al.   Nature Communications

Simultaneous inhibition of CXCR1/2, TGF-β, and PD-L1 remodels the tumor and its microenvironment to drive antitumor immunity

(2020) Lucas A Horn et al.   Journal for ImmunoTherapy of Cancer

Phase I study of bintrafusp alfa, a bifunctional fusion protein targeting TGF-β and PD-L1, in patients with pretreated biliary tract cancer

(2020) Changhoon Yoo et al.   Journal for ImmunoTherapy of Cancer

TGFβ biology in cancer progression and immunotherapy

(2020) Rik Derynck et al.   Nature Reviews Clinical Oncology

Bintrafusp alfa, a bifunctional fusion protein targeting TGF-β and PD-L1, in advanced squamous cell carcinoma of the head and neck: results from a phase I cohort

(2020) Byoung Chul Cho et al.   Journal for ImmunoTherapy of Cancer

Current perspectives on inhibitory SMAD7 in health and disease

(2020) Charlotte de Ceuninck van Capelle et al.   CRITICAL REVIEWS IN BIOCHEMISTRY AND MOLECULAR BIOLOGY

TGF-β suppresses type 2 immunity to cancer

(2020) Ming Liu et al.   NATURE

Cancer immunotherapy via targeted TGF-β signalling blockade in TH cells

(2020) Shun Li et al.   NATURE

Selective inhibition of TGF-β1 produced by GARP-expressing Tregs overcomes resistance to PD-1/PD-L1 blockade in cancer

(2020) Grégoire de Streel et al.   Nature Communications

Tumor mutational load predicts survival after immunotherapy across multiple cancer types

(2019) Robert M. Samstein et al.   NATURE GENETICS

α-PD-1 therapy elevates Treg/Th balance and increases tumor cell pSmad3 that are both targeted by α-TGFβ antibody to promote durable rejection and immunity in squamous cell carcinomas

(2019) E. Dodagatta-Marri et al.   Journal for ImmunoTherapy of Cancer

Specificity, versatility, and control of TGF-β family signaling

(2019) Rik Derynck et al.   Science Signaling

Five-year survival outcomes for patients with advanced melanoma treated with pembrolizumab in KEYNOTE-001

(2019) O Hamid et al.   ANNALS OF ONCOLOGY

Transforming Growth Factor-β Signaling in Immunity and Cancer

(2019) Eduard Batlle et al.   IMMUNITY

Novel Transforming Growth Factor Beta Receptor I Kinase Inhibitor Galunisertib ( LY 2157299) in Advanced Hepatocellular Carcinoma

(2019) Sandrine Faivre et al.   LIVER INTERNATIONAL

TGF-β-Mediated Epithelial-Mesenchymal Transition and Cancer Metastasis

(2019) Yang Hao et al.   INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES

TGFβ1 is essential for MSCs-CAFs differentiation and promotes HCT116 cells migration and invasion via JAK/STAT3 signaling

(2019) Hao-Xiang Tan et al.   OncoTargets and Therapy

Cancer-associated fibroblasts: an emerging target of anti-cancer immunotherapy

(2019) Tongyan Liu et al.   Journal of Hematology & Oncology

Five-Year Survival with Combined Nivolumab and Ipilimumab in Advanced Melanoma

(2019) James Larkin et al.   NEW ENGLAND JOURNAL OF MEDICINE

Tumor-derived TGF-β inhibits mitochondrial respiration to suppress IFN-γ production by human CD4+ T cells

(2019) Sarah Dimeloe et al.   Science Signaling

Targeting of the Cancer-Associated Fibroblast—T-Cell Axis in Solid Malignancies

(2019) Tom J. Harryvan et al.   Journal of Clinical Medicine

A Perspective on the Development of TGF-β Inhibitors for Cancer Treatment

(2019) Huynh et al.   Biomolecules

Transforming Growth Factor-beta signaling in αβ thymocytes promotes negative selection

(2019) Mark J. McCarron et al.   Nature Communications

Neoantigen-specific immunity in low mutation burden colorectal cancers of the consensus molecular subtype 4

(2019) Jitske van den Bulk et al.   Genome Medicine

Fc Effector Function Contributes to the Activity of Human Anti-CTLA-4 Antibodies

(2018) Frederick Arce Vargas et al.   CANCER CELL

A reappraisal of CTLA-4 checkpoint blockade in cancer immunotherapy

(2018) Xuexiang Du et al.   CELL RESEARCH

IDO1 in cancer: a Gemini of immune checkpoints

(2018) Lijie Zhai et al.   Cellular & Molecular Immunology

Focal Irradiation and Systemic TGFβ Blockade in Metastatic Breast Cancer

(2018) Silvia C. Formenti et al.   CLINICAL CANCER RESEARCH

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

Immune checkpoint blockade combined with IL-6 and TGF-β inhibition improves the therapeutic outcome of mRNA-based immunotherapy

(2018) Lukasz Bialkowski et al.   INTERNATIONAL JOURNAL OF CANCER

Tumor-Specific T-Cells Engineered to Overcome Tumor Immune Evasion Induce Clinical Responses in Patients With Relapsed Hodgkin Lymphoma

(2018) Catherine M. Bollard et al.   JOURNAL OF CLINICAL ONCOLOGY

TGFβ drives immune evasion in genetically reconstituted colon cancer metastasis

(2018) Daniele V. F. Tauriello et al.   NATURE

Human TGF-β1 deficiency causes severe inflammatory bowel disease and encephalopathy

(2018) Daniel Kotlarz et al.   NATURE GENETICS

Enhanced preclinical antitumor activity of M7824, a bifunctional fusion protein simultaneously targeting PD-L1 and TGF-β

(2018) Yan Lan et al.   Science Translational Medicine

Bifunctional immune checkpoint-targeted antibody-ligand traps that simultaneously disable TGFβ enhance the efficacy of cancer immunotherapy

(2018) Rajani Ravi et al.   Nature Communications

M7824, a novel bifunctional anti-PD-L1/TGFβ Trap fusion protein, promotes anti-tumor efficacy as monotherapy and in combination with vaccine

(2018) Karin M. Knudson et al.   OncoImmunology

Targeting the TGFβ pathway with galunisertib, a TGFβRI small molecule inhibitor, promotes anti-tumor immunity leading to durable, complete responses, as monotherapy and in combination with checkpoint blockade

(2018) Rikke B. Holmgaard et al.   Journal for ImmunoTherapy of Cancer

Contribution of NK cells to immunotherapy mediated by PD-1/PD-L1 blockade

(2018) Joy Hsu et al.   JOURNAL OF CLINICAL INVESTIGATION

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

(2018) Sanjeev Mariathasan et al.   NATURE

TGFBI Expressed by Bone Marrow Niche Cells and Hematopoietic Stem and Progenitor Cells Regulates Hematopoiesis

(2018) Sofieke E. Klamer et al.   STEM CELLS AND DEVELOPMENT

Stromal Fibroblasts Mediate Anti-PD-1 Resistance via MMP-9 and Dictate TGF-β Inhibitor Sequencing in Melanoma

(2018) Fei Zhao et al.   Cancer Immunology Research

Avelumab, an IgG1 anti-PD-L1 Immune Checkpoint Inhibitor, Triggers NK Cell-Mediated Cytotoxicity and Cytokine Production Against Triple Negative Breast Cancer Cells

(2018) Estefanía Paula Juliá et al.   Frontiers in Immunology

Resident memory T cells, critical components in tumor immunology

(2018) Fathia Mami-Chouaib et al.   Journal for ImmunoTherapy of Cancer

TGF-β-associated extracellular matrix genes link cancer-associated fibroblasts to immune evasion and immunotherapy failure

(2018) Ankur Chakravarthy et al.   Nature Communications

Autocrine TGFβ is a Survival Factor for Monocytes and Drives Immunosuppressive Lineage Commitment

(2018) Alba Gonzalez-Junca et al.   Cancer Immunology Research

CD4 + T Cell Help Confers a Cytotoxic T Cell Effector Program Including Coinhibitory Receptor Downregulation and Increased Tissue Invasiveness

(2017) Tomasz Ahrends et al.   IMMUNITY

The Cytokine TGF-β Promotes the Development and Homeostasis of Alveolar Macrophages

(2017) Xueyang Yu et al.   IMMUNITY

TGF-β in inflammatory bowel disease: a key regulator of immune cells, epithelium, and the intestinal microbiota

(2017) Sozaburo Ihara et al.   JOURNAL OF GASTROENTEROLOGY

Case Report

(2017) Maurizio Ghisoli et al.   JOURNAL OF PEDIATRIC HEMATOLOGY ONCOLOGY

Force interacts with macromolecular structure in activation of TGF-β

(2017) Xianchi Dong et al.   NATURE

Mismatch repair deficiency predicts response of solid tumors to PD-1 blockade

(2017) Dung T. Le et al.   SCIENCE

The Mechanisms of T Cell Selection in the Thymus

(2017) Hiroyuki Takaba et al.   TRENDS IN IMMUNOLOGY

Induction of resident memory T cells enhances the efficacy of cancer vaccine

(2017) Mevyn Nizard et al.   Nature Communications

TGFβ Signaling Intersects with CD103 Integrin Signaling to Promote T-Lymphocyte Accumulation and Antitumor Activity in the Lung Tumor Microenvironment

(2016) Marie Boutet et al.   CANCER RESEARCH

Surface Expression of TGFβ Docking Receptor GARP Promotes Oncogenesis and Immune Tolerance in Breast Cancer

(2016) Alessandra Metelli et al.   CANCER RESEARCH

Transforming Growth Factor β Drives Hemogenic Endothelium Programming and the Transition to Hematopoietic Stem Cells

(2016) Rui Monteiro et al.   DEVELOPMENTAL CELL

Phase II study of Vigil® DNA engineered immunotherapy as maintenance in advanced stage ovarian cancer

(2016) Jonathan Oh et al.   GYNECOLOGIC ONCOLOGY

Three-year Follow up of GMCSF/bi-shRNA furin DNA-transfected Autologous Tumor Immunotherapy (Vigil) in Metastatic Advanced Ewing's Sarcoma

(2016) Maurizio Ghisoli et al.   MOLECULAR THERAPY

Genomic analyses identify molecular subtypes of pancreatic cancer

(2016) Peter Bailey et al.   NATURE

A Phase II randomized study of galunisertib monotherapy or galunisertib plus lomustine compared with lomustine monotherapy in patients with recurrent glioblastoma

(2016) Alba A. Brandes et al.   NEURO-ONCOLOGY

TGF-β inhibits the activation and functions of NK cells by repressing the mTOR pathway

(2016) Sébastien Viel et al.   Science Signaling

Transcriptional Control by the SMADs

(2016) Caroline S. Hill   Cold Spring Harbor Perspectives in Biology

Signaling Receptors for TGF-β Family Members

(2016) Carl-Henrik Heldin et al.   Cold Spring Harbor Perspectives in Biology

TGF-β Signaling from Receptors to Smads

(2016) Akiko Hata et al.   Cold Spring Harbor Perspectives in Biology

TGF-β Family Signaling in the Control of Cell Proliferation and Survival

(2016) Yun Zhang et al.   Cold Spring Harbor Perspectives in Biology

Regulation of the Bioavailability of TGF-β and TGF-β-Related Proteins

(2016) Ian B. Robertson et al.   Cold Spring Harbor Perspectives in Biology

TGF-β and the TGF-β Family: Context-Dependent Roles in Cell and Tissue Physiology

(2016) Masato Morikawa et al.   Cold Spring Harbor Perspectives in Biology

TGF-β inhibits the activation and functions of NK cells by repressing the mTOR pathway

(2016) Sébastien Viel et al.   Science Signaling

TGF-  signaling in the control of hematopoietic stem cells

(2015) U. Blank et al.   BLOOD

Hematopoietic stem cells: concepts, definitions, and the new reality

(2015) C. J. Eaves   BLOOD

FcγRs Modulate the Anti-tumor Activity of Antibodies Targeting the PD-1/PD-L1 Axis

(2015) Rony Dahan et al.   CANCER CELL

Th17 Cell Pathway in Human Immunity: Lessons from Genetics and Therapeutic Interventions

(2015) Dhavalkumar D. Patel et al.   IMMUNITY

Mutations in a TGF-β Ligand, TGFB3, Cause Syndromic Aortic Aneurysms and Dissections

(2015) Aida M. Bertoli-Avella et al.   JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY

Stromal gene expression defines poor-prognosis subtypes in colorectal cancer

(2015) Alexandre Calon et al.   NATURE GENETICS

Stromal contribution to the colorectal cancer transcriptome

(2015) Claudio Isella et al.   NATURE GENETICS

The consensus molecular subtypes of colorectal cancer

(2015) Justin Guinney et al.   NATURE MEDICINE

Genomic correlates of response to CTLA-4 blockade in metastatic melanoma

(2015) E. M. Van Allen et al.   SCIENCE

Mutational landscape determines sensitivity to PD-1 blockade in non-small cell lung cancer

(2015) N. A. Rizvi et al.   SCIENCE

Monoclonal antibodies against GARP/TGF-β1 complexes inhibit the immunosuppressive activity of human regulatory T cells in vivo

(2015) Julia Cuende et al.   Science Translational Medicine

Id1 suppresses anti-tumour immune responses and promotes tumour progression by impairing myeloid cell maturation

(2015) Marianna Papaspyridonos et al.   Nature Communications

Cardiac Safety of TGF-β Receptor I Kinase Inhibitor LY2157299 Monohydrate in Cancer Patients in a First-in-Human Dose Study

(2014) Richard J. Kovacs et al.   Cardiovascular Toxicology

First-in-Human Dose Study of the Novel Transforming Growth Factor-β Receptor I Kinase Inhibitor LY2157299 Monohydrate in Patients with Advanced Cancer and Glioma

(2014) Jordi Rodon et al.   CLINICAL CANCER RESEARCH

Functional Heterogeneity of Cancer-Associated Fibroblasts from Human Colon Tumors Shows Specific Prognostic Gene Expression Signature

(2013) M. Herrera et al.   CLINICAL CANCER RESEARCH

Oncology Meets Immunology: The Cancer-Immunity Cycle

(2013) Daniel S. Chen et al.   IMMUNITY

CD19-Targeted T Cells Rapidly Induce Molecular Remissions in Adults with Chemotherapy-Refractory Acute Lymphoblastic Leukemia

(2013) R. J. Brentjens et al.   Science Translational Medicine

Thoracic aortic-aneurysm and dissection in association with significant mitral valve disease caused by mutations in TGFB2

(2012) Marjolijn Renard et al.   INTERNATIONAL JOURNAL OF CARDIOLOGY

TGF-β is responsible for NK cell immaturity during ontogeny and increased susceptibility to infection during mouse infancy

(2012) Jeffrey P Marcoe et al.   NATURE IMMUNOLOGY

TGFβ signalling in context

(2012) Joan Massagué   NATURE REVIEWS MOLECULAR CELL BIOLOGY

Indoleamine 2,3-dioxygenase is a signaling protein in long-term tolerance by dendritic cells

(2011) Maria T Pallotta et al.   NATURE IMMUNOLOGY

Human Tumour Immune Evasion via TGF-β Blocks NK Cell Activation but Not Survival Allowing Therapeutic Restoration of Anti-Tumour Activity

(2011) Erica B. Wilson et al.   PLoS One

Induction of Heart Valve Lesions by Small-Molecule ALK5 Inhibitors

(2011) Mark J. Anderton et al.   TOXICOLOGIC PATHOLOGY

Differentiation of Effector CD4 T Cell Populations

(2010) Jinfang Zhu et al.   Annual Review of Immunology

Eradication of B-lineage cells and regression of lymphoma in a patient treated with autologous T cells genetically engineered to recognize CD19

(2010) J. N. Kochenderfer et al.   BLOOD

TGF-β affects development and differentiation of human natural killer cell subsets

(2010) David S. J. Allan et al.   EUROPEAN JOURNAL OF IMMUNOLOGY

Overview of the immune response

(2010) David D. Chaplin   JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY

Polarization of Tumor-Associated Neutrophil Phenotype by TGF-β: “N1” versus “N2” TAN

(2009) Zvi G. Fridlender et al.   CANCER CELL

TGF-β1 dampens the susceptibility of dendritic cells to environmental stimulation, leading to the requirement for danger signals for activation

(2009) Tomoyuki Ohtani et al.   IMMUNOLOGY

TGF-β: A Master of All T Cell Trades

(2008) Ming O. Li et al.   CELL

Arginine regulation by myeloid derived suppressor cells and tolerance in cancer: mechanisms and therapeutic perspectives

(2008) Paulo C. Rodríguez et al.   IMMUNOLOGICAL REVIEWS