Baseline antibody profiles predict toxicity in melanoma patients treated with immune checkpoint inhibitors

Published on Dec 1, 2018in Journal of Translational Medicine4.10
· DOI :10.1186/s12967-018-1452-4
Michael Gowen2
Estimated H-index: 2
(NYU: New York University),
Keith M. Giles22
Estimated H-index: 22
(NYU: New York University)
+ 11 AuthorsIman Osman49
Estimated H-index: 49
(NYU: New York University)
Background Immune checkpoint inhibitors (anti-CTLA-4, anti-PD-1, or the combination) enhance anti-tumor immune responses, yielding durable clinical benefit in several cancer types, including melanoma. However, a subset of patients experience immune-related adverse events (irAEs), which can be severe and result in treatment termination. To date, no biomarker exists that can predict development of irAEs.
  • References (36)
  • Citations (11)
Published on Jun 1, 2018in Clinical Reviews in Allergy & Immunology7.33
Yvan Jamilloux14
Estimated H-index: 14
(University of Lyon),
Alexandre Belot19
Estimated H-index: 19
(University of Lyon)
+ 6 AuthorsThomas Henry30
Estimated H-index: 30
(University of Lyon)
The knowledge on systemic autoinflammatory disorders (SAID) is expanding rapidly and new signalling pathways are being decrypted. The concept of autoinflammation has been proposed since 1999, to define a group of diseases with abnormal innate immunity activation. Since then, more than 30 monogenic SAID have been described. In this review, we first describe inflammasomopathies and SAID related to the interleukin-1 pathway. Recent insights into the pathogenesis of familial Mediterranean fever and ...
Published on Dec 1, 2017in Nature Communications11.88
Nicolas Jacquelot11
Estimated H-index: 11
(French Institute of Health and Medical Research),
María Paula Roberti9
Estimated H-index: 9
(French Institute of Health and Medical Research)
+ 47 AuthorsYaron Meirow4
Estimated H-index: 4
(HUJI: Hebrew University of Jerusalem)
Immune checkpoint blockers (ICB) have become pivotal therapies in the clinical armamentarium against metastatic melanoma (MMel). Given the frequency of immune related adverse events and increasing use of ICB, predictors of response to CTLA-4 and/or PD-1 blockade represent unmet clinical needs. Using a systems biology-based approach to an assessment of 779 paired blood and tumor markers in 37 stage III MMel patients, we analyzed association between blood immune parameters and the functional immun...
Published on Nov 9, 2017in The New England Journal of Medicine70.67
Jeffrey S. Weber81
Estimated H-index: 81
(NYU: New York University),
Mario Mandalà41
Estimated H-index: 41
+ 31 AuthorsIván Márquez-Rodas17
Estimated H-index: 17
(Complutense University of Madrid)
BackgroundNivolumab and ipilimumab are immune checkpoint inhibitors that have been approved for the treatment of advanced melanoma. In the United States, ipilimumab has also been approved as adjuvant therapy for melanoma on the basis of recurrence-free and overall survival rates that were higher than those with placebo in a phase 3 trial. We wanted to determine the efficacy of nivolumab versus ipilimumab for adjuvant therapy in patients with resected advanced melanoma. MethodsIn this randomized,...
Published on Oct 3, 2017in Expert Opinion on Biological Therapy3.58
Oliver W. Hakenberg35
Estimated H-index: 35
(University of Rostock)
ABSTRACTIntroduction: The checkpoint inhibitor nivolumab has recently demonstrated effectiveness against metatstatic urothelial carcinoma. Nivolumab is a fully human monoclonal antibody blocking PD-1 and thereby enhancing antitumour immune mechanisms.Areas covered: In this review, the authors describe the treatment of metastatic bladder cancer with nivolumab against the background of the standard treatment with cisplatin-based chemotherapy which can prolong overall survival from 3–6 months in un...
Published on Sep 1, 2017in Cell36.22
Spencer C. Wei7
Estimated H-index: 7
(University of Texas MD Anderson Cancer Center),
Jacob H. Levine6
Estimated H-index: 6
(Kettering University)
+ 8 AuthorsDana Pe’er14
Estimated H-index: 14
(Kettering University)
Summary Immune-checkpoint blockade is able to achieve durable responses in a subset of patients; however, we lack a satisfying comprehension of the underlying mechanisms of anti-CTLA-4- and anti-PD-1-induced tumor rejection. To address these issues, we utilized mass cytometry to comprehensively profile the effects of checkpoint blockade on tumor immune infiltrates in human melanoma and murine tumor models. These analyses reveal a spectrum of tumor-infiltrating T cell populations that are highly ...
Published on Aug 1, 2017in Immunology and Cell Biology3.95
Gerard F. Hoyne25
Estimated H-index: 25
(University of Notre Dame Australia),
Hannah Elliott2
Estimated H-index: 2
(University of Notre Dame Australia)
+ 1 AuthorsCecilia M. Prêle15
Estimated H-index: 15
Idiopathic pulmonary fibrosis (IPF) is the most common of the idiopathic interstitial pneumonias. It is typically associated with extensive and progressive fibrosis, and is fatal and has limited treatment options. Characteristically IPF patients display large lymphocyte aggregates composed of CD3+ T cells and CD20+ B cells within the lung tissue that are located near sites of active fibrosis. In addition, IPF patients can have autoantibodies to a range of host antigens, suggesting a breakdown in...
Published on Mar 1, 2017in Ejso3.38
Cindy Franklin5
Estimated H-index: 5
(University of Duisburg-Essen),
Elisabeth Livingstone18
Estimated H-index: 18
(University of Duisburg-Essen)
+ 2 AuthorsDirk Schadendorf88
Estimated H-index: 88
(University of Duisburg-Essen)
Abstract Malignant melanoma contributes the majority of skin cancer related deaths and shows an increasing incidence in the past years. Despite all efforts of early diagnosis, metastatic melanoma still has a poor prognosis and remains a challenge for treating physicians. In recent years, improved knowledge of the pathophysiology and a better understanding of the role of the immune system in tumour control have led to the development and approval of several immunotherapies. Monoclonal antibodies ...
Published on Dec 1, 2016in BioDrugs4.90
Daphne Day3
Estimated H-index: 3
(OICR: Ontario Institute for Cancer Research),
Aaron Richard Hansen17
Estimated H-index: 17
(U of T: University of Toronto)
Immune checkpoint inhibitors (ICIs), including antibodies targeting cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) and programmed cell death protein-1 (PD-1), have shown durable treatment responses in multiple tumor types by enhancing antitumor immunity. However, removal of self-tolerance can induce autoimmunity and produce a unique immune-driven toxicity profile, termed immune-related adverse events (irAEs). As ICIs gain approval for a growing number of indications, it is imperative clini...
Published on Dec 1, 2016in Lancet Oncology35.39
Geoffrey T. Gibney21
Estimated H-index: 21
(MedStar Georgetown University Hospital),
Louis M Weiner1
Estimated H-index: 1
(MedStar Georgetown University Hospital),
Michael B. Atkins4
Estimated H-index: 4
(MedStar Georgetown University Hospital)
Summary The clinical development of checkpoint inhibitor-based immunotherapy has ushered in an exciting era of anticancer therapy. Durable responses can be seen in patients with melanoma and other malignancies. Although monotherapy with PD-1 or PD-L1 agents are typically well tolerated, the risk of immune-related adverse events increases with combination regimens. The development of predictive biomarkers is needed to optimise patient benefit, minimise risk of toxicities, and guide combination ap...
Published on Nov 10, 2016in The New England Journal of Medicine70.67
Alexander Eggermont40
Estimated H-index: 40
(AMU: Aix-Marseille University),
Vanna Chiarion-Sileni39
Estimated H-index: 39
+ 24 AuthorsJon M. Richards30
Estimated H-index: 30
BackgroundOn the basis of data from a phase 2 trial that compared the checkpoint inhibitor ipilimumab at doses of 0.3 mg, 3 mg, and 10 mg per kilogram of body weight in patients with advanced melanoma, this phase 3 trial evaluated ipilimumab at a dose of 10 mg per kilogram in patients who had undergone complete resection of stage III melanoma. MethodsAfter patients had undergone complete resection of stage III cutaneous melanoma, we randomly assigned them to receive ipilimumab at a dose of 10 mg...
Cited By11
Published on Dec 1, 2019in Clinical Proteomics2.89
Milena Music (U of T: University of Toronto), Antoninus Soosaipillai35
Estimated H-index: 35
(MSH: Mount Sinai Hospital, Toronto)
+ 3 AuthorsEleftherios P. Diamandis97
Estimated H-index: 97
Background Autoantibodies are produced when tolerance to self-antigens is broken and they can be mediators of tissue injury and systemic inflammation. They are excellent biomarkers because they are minimally invasive to screen and are highly abundant in serum due to limited proteolysis and slow clearance. Conventionally used methods of identifying autoantibodies in patient sera include indirect immunofluorescence, enzyme-linked immunoabsorbent assays (ELISAs) and protein microarrays. Here we pre...
Published on 2019in Current Opinion in Immunology7.67
Kavita M. Dhodapkar21
Estimated H-index: 21
(Emory University)
Immunotherapy of cancer with blockade of inhibitory immune checkpoints and adoptive cell therapies have led to impressive clinical responses in several cancers. However, with increasing utilization of these therapies, immune-related adverse events have emerged as a major obstacle. Herein I discuss recent insights into the immunobiology of these toxicities. Deeper understanding of the underlying pathogenic mechanisms, cellular and molecular pathways involved, similarities and differences with spo...
Published on Jun 1, 2019in Nature Reviews Clinical Oncology34.11
D. Ross Camidge56
Estimated H-index: 56
(CU: University of Colorado Boulder),
Robert C. Doebele41
Estimated H-index: 41
(CU: University of Colorado Boulder)
+ 0 AuthorsKeith M. Kerr (Aberd.: University of Aberdeen)
The era of personalized medicine for advanced-stage non-small-cell lung cancer (NSCLC) began when biomarker-based evidence of molecular pathway and/or oncogene addiction of the tumour became mandatory for the allocation of specific targeted therapies. More recently, the immunotherapy revolution, specifically, the development of immune-checkpoint inhibitors (ICIs), has dramatically altered the NSCLC treatment landscape. Herein, we compare and contrast the clinical development of immunotherapy and...
Published on May 13, 2019in Cells
Anne Largeot3
Estimated H-index: 3
Giulia Pagano + 2 AuthorsJerome Paggetti13
Estimated H-index: 13
Tumor-infiltrating lymphocytes are known to be critical in controlling tumor progression. While the role of T lymphocytes has been extensively studied, the function of B cells in this context is still ill-defined. In this review, we propose to explore the role of B cells in tumor immunity. First of all we define their dual role in promoting and inhibiting cancer progression depending on their phenotype. To continue, we describe the influence of different tumor microenvironment factors such as hy...
Published on May 1, 2019in Trends in Molecular Medicine11.03
Yu Fujita2
Estimated H-index: 2
(Jikei University School of Medicine),
Roberto Tinoco (UCI: University of California, Irvine)+ 2 AuthorsZe'ev Ronai70
Estimated H-index: 70
(DI: Discovery Institute)
Considerable progress has been made in understanding the contribution of E3 ubiquitin ligases to health and disease, including the pathogenesis of immunological disorders. Ubiquitin ligases exert exquisite spatial and temporal control over protein stability and function, and are thus crucial for the regulation of both innate and adaptive immunity. Given that immune responses can be both detrimental (autoimmunity) and beneficial (antitumor immunity), it is vital to understand how ubiquitin ligase...
Published on Mar 1, 2019in Nature Reviews Cancer51.85
Jonathan J. Havel10
Estimated H-index: 10
(MSK: Memorial Sloan Kettering Cancer Center),
Diego Chowell9
Estimated H-index: 9
(MSK: Memorial Sloan Kettering Cancer Center),
Timothy A. Chan64
Estimated H-index: 64
(MSK: Memorial Sloan Kettering Cancer Center)
Checkpoint inhibitor-based immunotherapies that target cytotoxic T lymphocyte antigen 4 (CTLA4) or the programmed cell death 1 (PD1) pathway have achieved impressive success in the treatment of different cancer types. Yet, only a subset of patients derive clinical benefit. It is thus critical to understand the determinants driving response, resistance and adverse effects. In this Review, we discuss recent work demonstrating that immune checkpoint inhibitor efficacy is affected by a combination o...
Published on Dec 1, 2018in Mammalian Genome2.34
Jessica Duarte4
Estimated H-index: 4
(La Trobe University),
Janique Peyper2
Estimated H-index: 2
(UCT: University of Cape Town),
Jonathan M. Blackburn20
Estimated H-index: 20
(UCT: University of Cape Town)
Recent developments in the immuno-oncology field strongly support a role for the immune system in both the prevention and progression of melanoma. Melanoma is a highly immunogenic cancer, including its ability to induce tumour antigen-specific B cell and antibody responses through largely unknown mechanisms. This review considers likely hypothetical mechanisms by which anti-tumour surveillance detects pre-cancerous cells and by which immune (including B cell and antibody) responses may be elicit...
Published on Dec 1, 2018in Journal for ImmunoTherapy of Cancer
Alice Horisberger1
Estimated H-index: 1
(UNIL: University of Lausanne),
Stefano La Rosa30
Estimated H-index: 30
(UNIL: University of Lausanne)
+ 4 AuthorsMichel Obeid8
Estimated H-index: 8
(UNIL: University of Lausanne)
The prevalence of esophageal stenosis caused by immune checkpoint inhibitors in the context of induced immune mucositis and esophagitis is extremely rare. We report the case of a patient with stage IV pulmonary adenocarcinoma treated for 6 months with nivolumab who developed bilateral sterile conjunctivitis followed by oropharyngeal mucositis and esophagitis complicated by a severe esophageal stenosis. The laryngeal margin and hypopharyngeal mucosa appeared highly inflammatory with fibrinous dep...
Published on Dec 1, 2018in Cancer immunology research8.62
Arabella Young2
Estimated H-index: 2
(UCSF: University of California, San Francisco),
Zoe Quandt4
Estimated H-index: 4
(UCSF: University of California, San Francisco),
Jeffrey A. Bluestone132
Estimated H-index: 132
(UCSF: University of California, San Francisco)
The explosion in novel cancer immunotherapies has resulted in extraordinary clinical successes in the treatment of multiple cancers. Checkpoint inhibitors (CPIs) that target negative regulatory molecules have become standard of care. However, with the growing use of CPIs, alone or in combination with chemotherapy, targeted therapies, or other immune modulators, a significant increase in immune-related adverse events (irAEs) has emerged. The wide-ranging and currently unpredictable spectrum of CP...
Published on Oct 1, 2018in Nature Reviews Rheumatology18.55
Leonard H. Calabrese9
Estimated H-index: 9
(Cleveland Clinic Lerner College of Medicine),
Cassandra Calabrese1
Estimated H-index: 1
(Cleveland Clinic Lerner College of Medicine),
Laura C. Cappelli6
Estimated H-index: 6
(Johns Hopkins University)
Immunotherapy has revolutionized the treatment of cancer, but a rapid rise in the use of the family of therapeutic agents known as checkpoint inhibitors (CPIs) is associated with a new group of immune-related adverse events (irAEs) in almost any organ system. Among these irAEs, rheumatic complications are common and seem to have features that are distinct from irAEs in other organ systems, including a highly variable time of clinical onset and the capacity to persist, possibly indefinitely, even...