S2724 Clinical Presentation, Treatment Strategies, and Chronic Sequelae of Immune Checkpoint Inhibitor-Mediated Cholangiopathy: A Case Study

Immunotherapy has been used as a first-line treatment for a variety of advanced tumors, allowing remarkable progress to be made in cancer treatment. Nonetheless, only a small number of patients can benefit from immune checkpoint inhibitor monotherapy. To improve the effect of immunotherapy, the underlying mechanism of combination therapy was investigated in the context of an intact human tumor immune microenvironment using mice with a human immune system (HIS) bearing human tumors. Herein, we summarize and discuss strategies for the development and use of HIS mice models in tumor immunotherapies. Most importantly, this review proposes a method of t11umor identification and classification in HIS mice based on the tumor-infiltrating lymphocytes and PD-L1 expression, and according to this classification, we propose different combination treatment strategies that can be utilized to enhance the effect of immunotherapy. Thus, we provide effective experimental schemes for tumor immunotherapy in HIS mice models.

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Differences in clinical presentation and outcome between immune checkpoint inhibitor-associated myocarditis and classical acute myocarditis: Same disease, distinct challenges to face

International Journal of Cardiology ◽

10.1016/j.ijcard.2019.08.038 ◽

2019 ◽

Vol 296 ◽

pp. 124-126 ◽

Cited By ~ 5

Author(s):

Giacomo Veronese ◽

Enrico Ammirati

Keyword(s):

Immune Checkpoint ◽

Immune Checkpoint Inhibitor ◽

Clinical Presentation ◽

Checkpoint Inhibitor ◽

Acute Myocarditis

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PD-1 Checkpoint Inhibitor Associated Autoimmune Encephalitis

Case Reports in Oncology ◽

10.1159/000477162 ◽

2017 ◽

Vol 10 (2) ◽

pp. 473-478 ◽

Cited By ~ 32

Author(s):

Stephanie Schneider ◽

Silke Potthast ◽

Paul Komminoth ◽

Guido Schwegler ◽

Steffen Böhm

Keyword(s):

Immune Checkpoint ◽

Immune Checkpoint Inhibitor ◽

Checkpoint Inhibitor ◽

Checkpoint Inhibitors ◽

Autoimmune Encephalitis ◽

Clinical Trial Data ◽

Substantial Improvement ◽

Antiepileptic Treatment ◽

Inhibitor Treatment

Objective: To report first-hand narrative experience of autoimmune encephalitis and to briefly review currently available evidence of autoimmune encephalitis in cancer patients treated with immune checkpoint inhibitors. Setting: A case study is presented on the management of a patient who developed autoimmune encephalitis during nivolumab monotherapy occurring after 28 weeks on anti-PD-1 monotherapy (nivolumab 3 mg/kg every 2 weeks) for non-small cell lung cancer. Results: No substantial improvement was observed by antiepileptic treatment. After administration of 80 mg methylprednisolone, neurologic symptoms disappeared within 24 h and the patient fully recovered. Conclusions: Immune checkpoint inhibitor treatment can lead to autoimmune encephalitis. Clinical trial data indicate a frequency of autoimmune encephalitis of ≥0.1 to <1% with a higher probability during combined or sequential anti-CTLA-4/anti-PD-1 therapy than during anti-PD-1 or anti-PD-L1 monotherapy. Further collection of evidence and translational research is warranted.

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Progress in the Application of Immune Checkpoint Inhibitor-Based Immunotherapy for Targeting Different Types of Colorectal Cancer

Frontiers in Oncology ◽

10.3389/fonc.2021.764618 ◽

2021 ◽

Vol 11 ◽

Author(s):

Rui He ◽

Yefang Lao ◽

Wenyan Yu ◽

Xiaohui Zhang ◽

Min Jiang ◽

...

Keyword(s):

Colorectal Cancer ◽

Immune Checkpoint ◽

Immune Checkpoint Inhibitor ◽

Checkpoint Inhibitor ◽

Rapid Development ◽

Treatment Strategies ◽

Basic Research ◽

Oncolytic Viruses ◽

Systematic Classification ◽

Different Types

Colorectal cancer (CRC), a common malignant disease, has the second highest mortality rate among all cancer types. Due to the diversity and heterogeneity of CRC, few effective treatment strategies have been developed in recent years, except for surgical resection. As immunotherapy has become a revolutionary treatment after surgery, along with chemoradiotherapy and targeted therapy, numerous basic research studies and clinical trials have been conducted on CRC. Therefore, immune checkpoint inhibitor (ICI) therapy has become the main anti-CRC immunotherapy method used at present. With the rapid development of biotechnology and cell research, an increasing number of monotherapy or combination therapy strategies using ICIs for CRC have been designed in recent years. Methods to classify and review ICI strategies for different types of CRC to better guide treatment are continuously investigated. However, the identification of why the ICIs would be more effective in targeting particular subtypes of CRC such as high microsatellite instability (MSI-H) is more important because of the different immune backgrounds in patients. This review intends to classify different subtypes of CRC and summarizes the basic and clinical studies on ICIs for each subtype of CRC currently available. In addition, we also attempt to briefly discuss the progress in immunotherapy methods other than ICI therapy, such as chemoimmunotherapy strategy, chimeric antigen receptor-modified T (CAR-T) cells, or immunotherapy based on oncolytic viruses. Finally, we provide a perspective on the development of immunotherapy in the treatment of CRC and attempt to propose a new systematic classification of CRC based on immunological strategies, which may improve guidance for the selection of immunotherapy strategies for different subtypes of CRC in the future.

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Case Series of Steroid-Resistant Immune Checkpoint Inhibitor Associated Myocarditis: A Comparative Analysis of Corticosteroid and Tofacitinib Treatment

Frontiers in Pharmacology ◽

10.3389/fphar.2021.770631 ◽

2021 ◽

Vol 12 ◽

Author(s):

Cong Wang ◽

Jinyi Lin ◽

Yan Wang ◽

David H. Hsi ◽

Jiahui Chen ◽

...

Keyword(s):

Comparative Analysis ◽

Immune Checkpoint ◽

Immune Checkpoint Inhibitor ◽

Checkpoint Inhibitor ◽

Troponin T ◽

Group Analysis ◽

Treatment Strategies ◽

Case Series ◽

Individualized Treatment ◽

Cardiac Biomarkers

Background: Immune checkpoint inhibitor (ICI)–associated myocarditis is an uncommon and potentially fatal immune-related adverse event (irAE). Although corticosteroids are recommended as the first-line treatment by current guidelines, patients still have variable responses to it, and the guidelines vary significantly in terms of treatment strategies.Objectives: In this study, we performed a retrospective analysis of ICI-associated myocarditis in our hospital to propose a new comparative analysis to aid individualized treatment.Methods: We reviewed detailed records of 24 patients with confirmed ICI-associated myocarditis in our hospital from July 1, 2019, to April 1, 2021. Although all the cases in our study received recommended initial corticosteroid treatment according to the guidelines, different responses to corticosteroid were observed during the process of subsequent corticosteroid tapering. Basing on troponin cardiac troponin T rebound during corticosteroid tapering, we propose a new classification analysis of ICI-associated myocarditis that included two subgroups: corticosteroid-sensitive (n = 8) and corticosteroid-resistant group (n = 16).Results: Compared with corticosteroid-sensitive patients, larger doses of corticosteroid, longer period of treatment, and higher mortality rate were found in corticosteroid-resistant patients. Corticosteroid-resistant patients were characterized by more prominent ptosis, muscle weakness, elevated cardiac biomarkers, creatine kinase, and hepatic enzymes levels than that in the corticosteroid-sensitive patients. Tofacitinib (5 mg twice a day) was used in 11 corticosteroid-resistant patients, with seven patients recovered from ICI-associated myocarditis, showing a promising therapeutic effect.Conclusion: Our group analysis of corticosteroid responsiveness in patients with ICI-associated myocarditis may help clinicians to apply individualized treatment in this high-risk cohort. In addition, tofacitinib could provide clinical benefits when used early in the corticosteroid-resistant patients and may provide a new option for the treatment of ICI-associated myocarditis.

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