☆ 4.6 Review

Effects of immune-related adverse events (irAEs) and their treatment on antitumor immune responses

IMMUNOLOGICAL REVIEWS (2023)

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Article Oncology

Association Between Rheumatic Autoantibodies and Immune-Related Adverse Events

Kristen Mathias et al.

Summary: This article examines the clinical utility of rheumatic autoantibodies (rhAbs) in diagnosing immune-related adverse events (irAEs). The study finds a significant association between rhAbs and rheumatic irAEs, and shows that irAEs are linked to better overall survival.

ONCOLOGIST (2023)

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Article Cell Biology

CD8+T cell-intrinsic IL-6 signaling promotes resistance to anti-PD-L1 immunotherapy

Mahrukh A. Huseni et al.

Summary: IL-6 is identified as a correlate of poor response to atezolizumab in clinical trials of advanced kidney, breast, and bladder cancers. In pre-clinical models, combined blockade of PD-L1 and IL-6 receptor (IL6R) has synergistic regression effects on tumors and improves anti-tumor CD8+ cytotoxic T lymphocyte (CTL) responses. Agents targeting IL-6 signaling could be potential partners for combination with immune checkpoint inhibitors (ICIs) in cancer patients.

CELL REPORTS MEDICINE (2023)

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Review Oncology

Immune-checkpoint inhibitors: long-term implications of toxicity

Douglas B. Johnson et al.

Summary: Immune-checkpoint inhibitors have improved outcomes for advanced-stage solid tumour patients, but they also carry the risk of chronic toxicities that can affect patients' quality of life. While evidence on chronic toxicities is limited, emerging evidence suggests that they may be more common than previously thought. These toxicities can affect various organ systems and may even lead to fatal outcomes. Research on the effects of immune-checkpoint blockade on other immune processes is also important for cancer survivors.

NATURE REVIEWS CLINICAL ONCOLOGY (2022)

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Article Oncology

Association between immune-related adverse event timing and treatment outcomes

David Hsiehchen et al.

Summary: The timing of immune-related adverse events (irAE) associated with immune checkpoint inhibitors (ICI) varies greatly. Late-onset irAE is associated with better clinical outcomes compared to early-onset irAE.

ONCOIMMUNOLOGY (2022)

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Article Oncology

Lower baseline autoantibody levels are associated with immune-related adverse events from immune checkpoint inhibition

Nilasha Ghosh et al.

Summary: Immune checkpoint inhibitors have shown success in treating advanced cancers but can also lead to immune-related adverse events (irAE). This study investigated the association between baseline autoantibodies and irAE development in patients receiving ICI therapy for melanoma. Results showed that lower autoantibody concentrations at baseline and a greater change in antibody concentration over time were associated with organ-specific irAE. Further research is needed to understand the role of autoantibodies in the pathogenesis of irAE.

JOURNAL FOR IMMUNOTHERAPY OF CANCER (2022)

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Review Biotechnology & Applied Microbiology

Emerging therapeutic opportunities for integrin inhibitors

R. J. Slack et al.

Summary: Integrins play crucial roles in cell adhesion and signaling, making them potential therapeutic targets. This review discusses the challenges and development of integrin inhibitors, particularly those targeting integrins with an alpha v-subunit. Opportunities exist for learning from previous trials and exploring new modalities in integrin drug design.

NATURE REVIEWS DRUG DISCOVERY (2022)

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Article Multidisciplinary Sciences

Distinct molecular and immune hallmarks of inflammatory arthritis induced by immune checkpoint inhibitors for cancer therapy

Sang T. Kim et al.

Summary: Immune checkpoint inhibitors can cause arthritis as an immune-related adverse event (irAE). Managing arthritis-irAE is difficult because standard treatments for arthritis should not hinder antitumor immunity. This study analyzed blood and synovial fluid samples from 20 patients with arthritis-irAE and found a prominent Th1-CD8(+) T cell axis in both blood and inflamed joints. The clonally expanded CX3CR1(hi) CD8(+) T cells in blood and CXCR3(hi) CD8(+) T cells in synovial fluid had significant TCR repertoire overlap. This research provides insights into the mechanisms, predictive biomarkers, and therapeutic targets for arthritis-irAE.

NATURE COMMUNICATIONS (2022)

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Article Oncology

Impact of immune-related adverse events on the therapeutic efficacy of pembrolizumab in urothelial carcinoma: a multicenter retrospective study using time-dependent analysis

Taketo Kawai et al.

Summary: In this retrospective multicenter study, the association between the incidence of immune-related adverse events (irAEs) and the efficacy of pembrolizumab in urothelial carcinoma (UC) was assessed using time-dependent analysis. The study found that the occurrence of irAEs, especially grade 1-2 irAEs, could be a significant predictor of favorable prognoses in patients with UC who have undergone pembrolizumab treatment.

JOURNAL FOR IMMUNOTHERAPY OF CANCER (2022)

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Article Oncology

Reversal of immune-checkpoint inhibitor fulminant myocarditis using personalized-dose-adjusted abatacept and ruxolitinib: proof of concept

Lee S. Nguyen et al.

Summary: This article describes a case in which nearly lethal immune-checkpoint inhibitor (ICI)-induced myocarditis was reversed by the treatment of abatacept with adjusted dosage. This provides a basis for personalized treatment of patients with severe ICI adverse events.

JOURNAL FOR IMMUNOTHERAPY OF CANCER (2022)

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Article Multidisciplinary Sciences

T cells specific for α-myosin drive immunotherapy-related myocarditis

Margaret L. Axelrod et al.

Summary: Immune checkpoint inhibitors (ICIs) used in anticancer therapy are challenged by immune-related adverse events, such as myocarditis. This study investigates the pathogenesis of ICI-associated myocarditis (ICI-MC) and identifies CD8(+)T cells as the major cell population involved. α-myosin, a cardiac-specific protein, is identified as a potential autoantigen in ICI-MC. Understanding the mechanisms of ICI-MC could lead to new strategies for preventing and treating ICI toxicity.

NATURE (2022)

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Review Oncology

Analysis of the association between prospectively collected immune-related adverse events and survival in patients with solid tumor treated with immune-checkpoint blockers, taking into account immortal-time bias

Maria Kfoury et al.

Summary: This study conducted an observational study on real-life data of patients treated with immune checkpoint blockers for melanoma and non-small cell lung cancer, confirming the association between immune-related adverse events and improved survival using a time-varying Cox regression model.

CANCER TREATMENT REVIEWS (2022)

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Article Medicine, Research & Experimental

Tertiary lymphoid structure signatures are associated with immune checkpoint inhibitor related acute interstitial nephritis

Shailbala Singh et al.

JCI Insight (2022)

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Article Oncology

Baseline Serum Autoantibody Signatures Predict Recurrence and Toxicity in Melanoma Patients Receiving Adjuvant Immune Checkpoint Blockade

Paul Johannet et al.

Summary: This study found that baseline serum autoantibody signatures predicted recurrence and severe toxicity in patients treated with adjuvant immunotherapy.

CLINICAL CANCER RESEARCH (2022)

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Meeting Abstract Oncology

VEDOLIZUMAB PLUS ANTI-PD1 ANTIBODY IN ADVANCED MELANOMA PATIENTS WITH INFLAMMATORY ENTEROCOLITIS

Asad Javed et al.

JOURNAL FOR IMMUNOTHERAPY OF CANCER (2022)

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Review Rheumatology

Checkpoint Inhibitor-Associated Arthritis A Systematic Review of Case Reports and Case Series

Nilasha Ghosh et al.

Summary: The study found that half of reported cases of immune checkpoint inhibitor-associated arthritis present as polyarthritis (often RA-like), but only 9% test positive for serological markers. Polymyalgia rheumatica is also common in these cases. Most patients respond to steroids, but 50% require additional medications.

JCR-JOURNAL OF CLINICAL RHEUMATOLOGY (2021)

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Editorial Material Gastroenterology & Hepatology

Efficacy and Outcome of Tofacitinib in Immune checkpoint Inhibitor Colitis

Shrinivas Bishu et al.

GASTROENTEROLOGY (2021)

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Article Pathology

Liver biopsy findings in patients on immune checkpoint inhibitors

Justine V. Cohen et al.

Summary: Immune checkpoint inhibitors (ICI) can elicit durable responses in various malignancies but can also lead to immune-related adverse events. This study aimed to evaluate the inflammation patterns in liver biopsies of patients on ICIs, and found that hepatitic pattern was the most common. Patients with a cholangitic pattern often had competing causes for liver function abnormalities, such as disease progression or concomitant chemotherapy.

MODERN PATHOLOGY (2021)

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Article Oncology

Effect of corticosteroids on the outcome of patients with advanced non-small cell lung cancer treated with immune-checkpoint inhibitors

Marcus Skribek et al.

Summary: The study found that corticosteroid administration for immune-related adverse events (irAEs) did not impact overall survival (OS), while using steroids for cancer-related symptom palliation was an independent predictor for shorter OS. The timeline of steroid administration did not affect OS in the cohort.

EUROPEAN JOURNAL OF CANCER (2021)

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Article Oncology

Interleukin-6 blockade for prophylaxis and management of immune-related adverse events in cancer immunotherapy

Florentia Dimitriou et al.

Summary: The study showed that tocilizumab, an anti-interleukin-6 receptor monoclonal antibody, demonstrated effectiveness in treating or preventing autoimmune irAE in patients receiving ICIs. Tocilizumab improved clinical outcomes and C-reactive protein levels, while being well tolerated.

EUROPEAN JOURNAL OF CANCER (2021)

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Article Oncology

A Genetic Mouse Model Recapitulates Immune Checkpoint Inhibitors-Associated Myocarditis and Supports a Mechanism-Based Therapeutic Intervention

Spencer C. Wei et al.

Summary: This study presents a robust preclinical model of ICI-associated myocarditis that recapitulates the clinical syndrome. Using this model, researchers demonstrate that CTLA4 and PD-1 (ICI targets) functionally interact in the development of myocarditis, and intervention with CTLA4-Ig (abatacept) attenuates myocarditis, providing mechanistic rationale and preclinical support for therapeutic clinical studies.

CANCER DISCOVERY (2021)

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Article Immunology

Global analysis of shared T cell specificities in human non-small cell lung cancer enables HLA inference and antigen discovery

Shin-Heng Chiou et al.

Summary: Through analyzing a large number of T cell receptor sequences, we identified T cell receptors with shared antigen specificity in a subset of non-small cell lung cancer patients and identified some specificity groups enriched in tumors. Using a yeast peptide-HLA display library, we confirmed the antigenic epitopes of one tumor-enriched specificity group, indicating that pathogen cross-reactivity may be a feature of multiple cancers.

IMMUNITY (2021)

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Article Cell Biology

Epitope spreading toward wild-type melanocyte-lineage antigens rescues suboptimal immune checkpoint blockade responses

Jennifer A. Lo et al.

Summary: Studies suggest that patients responding to immune checkpoint inhibitors typically have higher levels of tumor-specific neoantigens and higher expression of pigmentation-related genes in tumors. Expansion of CD8(+) T cells specific for melanocyte antigens was observed only in patients responding to anti-PD-1 therapy, indicating potential breakdown of tolerance toward tumor-lineage self-antigens. Epitope spreading toward wild-type tumor-lineage self-antigens represents a common pathway for successful response to ICI.

SCIENCE TRANSLATIONAL MEDICINE (2021)

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Editorial Material Oncology

Interleukin-1 in tumor progression, therapy, and prevention

Cecilia Garlanda et al.

Summary: IL-1 plays a crucial role in inflammation and tumor progression, and targeting IL-1 may be considered for treating selected human tumors and in prevention and interception settings based on preclinical models and genetic associations.

CANCER CELL (2021)

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Article Oncology

Differential influence of antibiotic therapy and other medications on oncological outcomes of patients with non-small cell lung cancer treated with first-line pembrolizumab versus cytotoxic chemotherapy

Alessio Cortellini et al.

Summary: The study reveals the negative impact of antibiotics (ATB) on pembrolizumab monotherapy outcomes in NSCLC, while corticosteroids and proton pump inhibitors (PPIs) may worsen baseline performance status. These findings highlight the underlying immune-modulatory effects of these concomitant medications.

JOURNAL FOR IMMUNOTHERAPY OF CANCER (2021)

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Article Oncology

Early Use of High-Dose Glucocorticoid for the Management of irAE Is Associated with Poorer Survival in Patients with Advanced Melanoma Treated with Anti-PD-1 Monotherapy

Xue Bai et al.

Summary: A multicenter retrospective analysis found that early high-dose GCC use was associated with poorer survival outcomes in melanoma patients after anti-PD-1 monotherapy, highlighting the need for cautious use of GCC. These findings were validated in a combined validation cohort, confirming the association between high-dose GCC use and worse prognosis.

CLINICAL CANCER RESEARCH (2021)

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Review Medicine, General & Internal

Tocilizumab for the treatment of immune-related adverse events: a systematic literature review and a multicentre case series

Corrado Campochiaro et al.

Summary: Research indicates that tocilizumab shows efficacy and safety in treating immune-related adverse events caused by immune checkpoint inhibitors, and a combined approach with ICI is suggested for effective management of irAEs without compromising the oncologic response.

EUROPEAN JOURNAL OF INTERNAL MEDICINE (2021)

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Article Oncology

Development of preclinical and clinical models for immune-related adverse events following checkpoint immunotherapy: a perspective from SITC and AACR

Nicholas L. Bayless et al.

Summary: Recent advances in cancer immunotherapy have revolutionized cancer treatment strategies, but the increasing incidence of immune-related adverse events is now limiting their overall benefits. Understanding the key mechanisms driving these adverse events is crucial for preventing and improving their treatment, and further research and specific recommendations are needed in this area.

JOURNAL FOR IMMUNOTHERAPY OF CANCER (2021)

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Article Oncology

Society for Immunotherapy of Cancer (SITC) clinical practice guideline on immune checkpoint inhibitor-related adverse events

Julie R. Brahmer et al.

Summary: ICIs are standard treatments for cancer, but come with risks of immune-related adverse events. The SITC convened an expert panel to develop guidelines for managing irAEs, aiming to improve patient outcomes through evidence-based recommendations.

JOURNAL FOR IMMUNOTHERAPY OF CANCER (2021)

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Article Pathology

Immune checkpoint inhibitor associated myocarditis occurs in both high-grade and low-grade forms

Samantha N. Champion et al.

MODERN PATHOLOGY (2020)

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Article Oncology

Immune Checkpoint Inhibitor Therapy in Patients With Preexisting Inflammatory Bowel Disease

Hamzah Abu-Sbeih et al.

JOURNAL OF CLINICAL ONCOLOGY (2020)

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Article Multidisciplinary Sciences

Tertiary lymphoid structures improve immunotherapy and survival in melanoma

Rita Cabrita et al.

NATURE (2020)

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Article Oncology

Association Between Immune-Related Adverse Events and Recurrence-Free Survival Among Patients With Stage III Melanoma Randomized to Receive Pembrolizumab or Placebo A Secondary Analysis of a Randomized Clinical Trial

Alexander M. M. Eggermont et al.

JAMA ONCOLOGY (2020)

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Article Oncology

Immune Checkpoint Inhibitor Rechallenge After Immune-Related Adverse Events in Patients With Cancer

Charles Dolladille et al.

JAMA ONCOLOGY (2020)

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Article Biochemistry & Molecular Biology

Molecular Pathways of Colon Inflammation Induced by Cancer Immunotherapy

Adrienne M. Luoma et al.

CELL (2020)

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Article Medicine, Research & Experimental

Cellular analysis of bronchoalveolar lavage fluid to narrow differential diagnosis of checkpoint inhibitor-related pneumonitis in metastatic melanoma

Sabino Strippoli et al.

JOURNAL OF TRANSLATIONAL MEDICINE (2020)

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Article Oncology

Multisystem Immune-Related Adverse Events Associated With Immune Checkpoint Inhibitors for Treatment of Non-Small Cell Lung Cancer

Bairavi Shankar et al.

JAMA ONCOLOGY (2020)

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Article Oncology

Efficacy and immune-related adverse event associations in avelumab-treated patients

Karen Kelly et al.

JOURNAL FOR IMMUNOTHERAPY OF CANCER (2020)

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Article Multidisciplinary Sciences

A defined commensal consortium elicits CD8 T cells and anti-cancer immunity

Takeshi Tanoue et al.

NATURE (2019)

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Article Oncology

Myocarditis in Cynomolgus Monkeys Following Treatment with Immune Checkpoint Inhibitors

Changhua Ji et al.

CLINICAL CANCER RESEARCH (2019)

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Article Immunology

Intratumoral Activity of the CXCR3 Chemokine System Is Required for the Efficacy of Anti-PD-1 Therapy

Melvyn T. Chow et al.

IMMUNITY (2019)

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Article Multidisciplinary Sciences

Prophylactic TNF blockade uncouples efficacy and toxicity in dual CTLA-4 and PD-1 immunotherapy

Elisabeth Perez-Ruiz et al.

NATURE (2019)

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Review Oncology

Adverse effects of immune-checkpoint inhibitors: epidemiology, management and surveillance

Filipe Martins et al.

NATURE REVIEWS CLINICAL ONCOLOGY (2019)

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Review Oncology

Treatment-Related Adverse Events of PD-1 and PD-L1 Inhibitors in Clinical Trials A Systematic Review and Meta-analysis

Yucai Wang et al.

JAMA ONCOLOGY (2019)

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Article Oncology

Association of Checkpoint Inhibitor-Induced Toxic Effects With Shared Cancer and Tissue Antigens in Non-Small Cell Lung Cancer

Fiamma Berner et al.

JAMA ONCOLOGY (2019)

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Article Oncology

Circulating Cytokines Predict Immune-Related Toxicity in Melanoma Patients Receiving Anti-PD-1-Based Immunotherapy

Su Y. Lim et al.

CLINICAL CANCER RESEARCH (2019)

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Article Oncology

Differential effects of corticosteroids and anti-TNF on tumor-specific immune responses: implications for the management of irAEs

Arianna Draghi et al.

INTERNATIONAL JOURNAL OF CANCER (2019)

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Article Oncology

New therapeutic perspectives to manage refractory immune checkpoint-related toxicities

Filipe Martins et al.

LANCET ONCOLOGY (2019)

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Article Oncology

Complete response of metastatic melanoma in a patient with Crohn's disease simultaneously receiving anti-47 and anti-PD1 antibodies

Christopher C. Frohne et al.

JOURNAL FOR IMMUNOTHERAPY OF CANCER (2019)

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Article Oncology

High-dose glucocorticoids for the treatment of ipilimumab-induced hypophysitis is associated with reduced survival in patients with melanoma

Alexander T. Faje et al.

CANCER (2018)

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Article Oncology

Safety of Programmed Death-1 Pathway Inhibitors Among Patients With Non-Small-Cell Lung Cancer and Preexisting Autoimmune Disorders

Giulia C. Leonardi et al.

JOURNAL OF CLINICAL ONCOLOGY (2018)

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Article Oncology

Early Use of Systemic Corticosteroids in Patients with Advanced NSCLC Treated with Nivolumab

Susan C. Scott et al.

JOURNAL OF THORACIC ONCOLOGY (2018)

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Review Medicine, General & Internal

Immune-Related Adverse Events Associated with Immune Checkpoint Blockade

Michael A. Postow et al.

NEW ENGLAND JOURNAL OF MEDICINE (2018)

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Article Oncology

Impact of Baseline Steroids on Efficacy of Programmed Cell Death-1 and Programmed Death-Ligand 1 Blockade in Patients With Non-Small-Cell Lung Cancer

Kathryn C. Arbour et al.

JOURNAL OF CLINICAL ONCOLOGY (2018)

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Article Multidisciplinary Sciences

Bystander CD8+ T cells are abundant and phenotypically distinct in human tumour infiltrates

Yannick Simoni et al.

NATURE (2018)

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Review Oncology

Fatal Toxic Effects Associated With Immune Checkpoint Inhibitors A Systematic Review and Meta-analysis

Daniel Y. Wang et al.

JAMA ONCOLOGY (2018)

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Review Immunology

The diverse functions of the PD1 inhibitory pathway

Arlene H. Sharpe et al.

NATURE REVIEWS IMMUNOLOGY (2018)

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Article Oncology

Angiopoietin-2 as a Biomarker and Target for Immune Checkpoint Therapy

Xinqi Wu et al.

CANCER IMMUNOLOGY RESEARCH (2017)

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Article Oncology

Ipilimumab 10 mg/kg versus ipilimumab 3 mg/kg in patients with unresectable or metastatic melanoma: a randomised, double-blind, multicentre, phase 3 trial

Paolo A. Ascierto et al.

LANCET ONCOLOGY (2017)

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Article Medicine, General & Internal

Overall Survival with Combined Nivolumab and Ipilimumab in Advanced Melanoma

J. D. Wolchok et al.

NEW ENGLAND JOURNAL OF MEDICINE (2017)

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Letter Medicine, General & Internal

Reversal of Autoimmune Toxicity and Loss of Tumor Response by Interleukin-17 Blockade

Khashayar Esfahani et al.

NEW ENGLAND JOURNAL OF MEDICINE (2017)

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Review Oncology

Immune and Molecular Correlates in Melanoma Treated With Immune Checkpoint Blockade

Elizabeth H. Byrne et al.

CANCER (2017)

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Article Medicine, General & Internal

Fulminant Myocarditis with Combination Immune Checkpoint Blockade

Douglas B. dbj Johnson et al.

NEW ENGLAND JOURNAL OF MEDICINE (2016)

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Article Immunology

Clonal Deletion Prunes but Does Not Eliminate Self-Specific αβ CD8+ T Lymphocytes

Wong Yu et al.

IMMUNITY (2015)

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Article Oncology

Challenges of Guarantee-Time Bias

Anita Giobbie-Hurder et al.

JOURNAL OF CLINICAL ONCOLOGY (2013)

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Article Medicine, General & Internal

Case reports of heart failure after therapy with a tumor necrosis factor antagonist

HJ Kwon et al.

ANNALS OF INTERNAL MEDICINE (2003)

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