scholarly journals Role of Cardiac Imaging in the Diagnosis of Immune Checkpoints Inhibitors Related Myocarditis

2021 ◽  
Vol 11 ◽  
Author(s):  
Stéphane Ederhy ◽  
Joe-Elie Salem ◽  
Laurent Dercle ◽  
Abrar Saqif Hasan ◽  
Marion Chauvet-Droit ◽  
...  
Keyword(s):  
Paradigm Shift ◽  
Checkpoint Inhibitors ◽  
Clinical Syndrome ◽  
Immune Checkpoints ◽  
Patients With Cancer ◽  
High Fatality Rate ◽  
Clinical Scenarios ◽  
Low Incidence ◽  
Electrocardiogram Ecg

Immune checkpoint inhibitors (ICI) have constituted a paradigm shift in the management of patients with cancer. Their administration is associated with a new spectrum of immune-related toxicities that can affect any organ. In patients treated with ICI, cardiovascular toxicities, particularly myocarditis, occur with a low incidence (<1%) but with a high fatality rate (30−50%). ICI-related myocarditis has been attributed to an immune infiltration, comprising of T-cells that are positive for CD3+, CD4+, CD8+, and macrophages that are positive for CD68. The diagnosis remains challenging and is made based on clinical syndrome, an electrocardiogram (ECG), biomarker data, and imaging criteria. In most clinical scenarios, endomyocardial biopsy plays a pivotal role in diagnosis, while cardiac magnetic resonance imaging (cMRI) has limitations that should be acknowledged. In this review, we discuss the role of medical imaging in optimizing the management of ICI related myocarditis, including diagnosis, prognostication, and treatment decisions.

scholarly journals Immune Checkpoint Inhibitor Nephrotoxicity: Update 2020

Kidney360 ◽  
2020 ◽  
Vol 1 (2) ◽  
pp. 130-140 ◽  
Author(s):  
Shruti Gupta ◽  
Frank B. Cortazar ◽  
Leonardo V. Riella ◽  
David E. Leaf
Keyword(s):  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitors ◽  
Solid Organ Transplantation ◽  
Treatment Strategies ◽  
Solid Organ ◽  
Diagnostic Uncertainty ◽  
Patients With Cancer ◽  
Underlying Malignancy

Immune checkpoint inhibitors (ICPIs) have transformed the landscape of oncology, but are associated with a variety of autoimmune adverse events, including AKI. ICPI-associated AKI (ICPI-AKI) is emerging as an increasingly frequent cause of AKI in patients with cancer, and poses unique diagnostic and management challenges to clinicians who care for these patients. In this review, we describe the incidence and risk factors for ICPI-AKI, including proton pump inhibitor use, CKD, and combination immunotherapy. We discuss the limitations of the various definitions used for ICPI-AKI in prior studies, and propose a novel classification system (definite, probable, and possible ICPI-AKI) that recognizes the diagnostic uncertainty inherent in many cases. We discuss the key clinicopathologic features and treatment strategies for ICPI-AKI, including the role of kidney biopsy versus empirical treatment with steroids. We also explore the under-studied area of ICPI use in the setting of solid organ transplantation, where nephrologists and oncologists must balance the risk of rejection versus treating the underlying malignancy. Finally, we summarize existing data on the role of ICPI rechallenge after an episode of ICPI-AKI.

scholarly journals Listeriosis during Pregnancy: A Public Health Concern

2013 ◽  
Vol 2013 ◽  
pp. 1-6 ◽  
Author(s):  
Teresa Mateus ◽  
Joana Silva ◽  
Rui L. Maia ◽  
Paula Teixeira
Keyword(s):  
Pregnant Women ◽  
Fetal Death ◽  
Foodborne Pathogen ◽  
Neonatal Morbidity ◽  
Health Concern ◽  
Prevention Measures ◽  
High Fatality Rate ◽  
The Usa ◽  
Low Incidence

Listeria was first described in 1926 by Murray, Webb, and Swann, who discovered it while investigating an epidemic infection among laboratory rabbits and guinea pigs. The role of Listeria monocytogenes as a foodborne pathogen was definitively recognized during the 1980s. This recognition was the consequence of a number of epidemic human outbreaks due to the consumption of contaminated foods, in Canada, in the USA and in Europe. Listeriosis is especially severe in immunocompromised individuals such as pregnant women. The disease has a low incidence of infection, although this is undeniably increasing, with a high fatality rate amongst those infected. In pregnant women listeriosis may cause abortion, fetal death, or neonatal morbidity in the form of septicemia and meningitis. Improved education concerning the disease, its transmission, and prevention measures for immunocompromised individuals and pregnant women has been identified as a pressing need.

scholarly journals Current Progress and Future Perspectives of Immune Checkpoint in Cancer and Infectious Diseases

2021 ◽  
Vol 12 ◽  
Author(s):  
Xin Cai ◽  
Huajie Zhan ◽  
Yuguang Ye ◽  
Jinjin Yang ◽  
Minghui Zhang ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Immune Checkpoint ◽  
Current Knowledge ◽  
Checkpoint Inhibitors ◽  
Single Agent ◽  
Immune Checkpoint Blockade ◽  
Immune Checkpoints ◽  
Microbial Infection ◽  
Antiviral Immune Response

The inhibitory regulators, known as immune checkpoints, prevent overreaction of the immune system, avoid normal tissue damage, and maintain immune homeostasis during the antimicrobial or antiviral immune response. Unfortunately, cancer cells can mimic the ligands of immune checkpoints to evade immune surveillance. Application of immune checkpoint blockade can help dampen the ligands expressed on cancer cells, reverse the exhaustion status of effector T cells, and reinvigorate the antitumor function. Here, we briefly introduce the structure, expression, signaling pathway, and targeted drugs of several inhibitory immune checkpoints (PD-1/PD-L1, CTLA-4, TIM-3, LAG-3, VISTA, and IDO1). And we summarize the application of immune checkpoint inhibitors in tumors, such as single agent and combination therapy and adverse reactions. At the same time, we further discussed the correlation between immune checkpoints and microorganisms and the role of immune checkpoints in microbial-infection diseases. This review focused on the current knowledge about the role of the immune checkpoints will help in applying immune checkpoints for clinical therapy of cancer and other diseases.

scholarly journals BTLA-HVEM Couple in Health and Diseases: Insights for Immunotherapy in Lung Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Clemence Demerlé ◽  
Laurent Gorvel ◽  
Daniel Olive
Keyword(s):  
Lung Cancer ◽  
Cancer Progression ◽  
Immune Escape ◽  
Checkpoint Inhibitors ◽  
Immune Checkpoints ◽  
Tumor Immune Escape ◽  
Promising Target ◽  
Tnf Receptor Family ◽  
Receptor Family

Lung cancer is the leading cause of cancer deaths worldwide. Immunotherapies (IT) have been rapidly approved for lung cancer treatment after the spectacular results in melanoma. Responses to the currently used checkpoint inhibitors are strikingly good especially in metastatic diseases. However, durable responses are observed in only 25% of cases. Consequently, there is an urgent need for new immunotherapy targets. Among the multiple checkpoints involved in the tumor immune escape, the BTLA-HVEM couple appears to be a promising target. BTLA (B- and T- Lymphocyte Attenuator) is a co-inhibitory receptor mainly expressed by B and T cells, repressing the activation signal transduction. BTLA shares similarities with other immune checkpoints such as PD-1 and CTLA-4 which are the targets of the currently used immunotherapies. Furthermore, BTLA expression points out terminally exhausted and dysfunctional lymphocytes, and correlates with lung cancer progression. The ligand of BTLA is HVEM (Herpes Virus Entry Mediator) which belongs to the TNF receptor family. Often described as a molecular switch, HVEM is constitutively expressed by many cells, including cells from tumor and healthy tissues. In addition, HVEM seems to be involved in tumor immuno-evasion, especially in lung tumors lacking PD-L1 expression. Here, we propose to review the role of BTLA-HVEM in immuno-escape in order to highlight its potential for designing new immunotherapies.

scholarly journals Is There a Role for Programmed Death Ligand-1 Testing and Immunotherapy in Colorectal Cancer With Microsatellite Instability? Part II—The Challenge of Programmed Death Ligand-1 Testing and Its Role in Microsatellite Instability-High Colorectal Cancer

2017 ◽  
Vol 142 (1) ◽  
pp. 26-34 ◽  
Author(s):  
Esmeralda Celia Marginean ◽  
Barbara Melosky
Keyword(s):  
Colorectal Cancer ◽  
Immune Response ◽  
Microsatellite Instability ◽  
Therapeutic Potential ◽  
Checkpoint Inhibitors ◽  
Death Receptor ◽  
Immune Checkpoints ◽  
Programmed Death Ligand 1 ◽  
Programmed Death

Context.— The world of oncology has changed dramatically in the past few years with the introduction of checkpoint inhibitors and immunotherapy. The promising findings of a small, phase 2 clinical trial that led to the US Food and Drug Administration breakthrough designation and approval of the anti–programmed death receptor-1 (PD-1) drug pembrolizumab (Keytruda, Merck, Kenilworth, New Jersey) to treat metastatic/refractory microsatellite instability–high colorectal cancer (CRC) has significantly boosted interest in immunomodulatory therapies in microsatellite instability–high CRC. Objectives.— To review the immune response to cancer and the role of immune checkpoints, focusing on the technical and interpretation challenges of PD-1/programmed death ligand-1 (PD-L1) testing by pathologists and the clinical implications of the test and the therapeutic potential of treating CRC with checkpoint inhibitors. Data Sources.— A PubMed review was performed of articles pertaining to CRC, microsatellite instability and mismatch repair systems, molecular classification, immune response, PD-1/PD-L1, and immunotherapy. Conclusions.— Exciting success with anti–PD-1/PD-L1 and anticytotoxic T-lymphocyte–associated protein 4 (CTLA4) checkpoint inhibitors has already been reported in melanoma and in lung and renal carcinomas. Recently, microsatellite instability–high CRCs, expressing PD-L1 by immunohistochemistry, regardless of the level of that PD-L1 expression, appeared to respond to checkpoint blockades with anti–PD-1 or anti–PD-L1 agents, whereas microsatellite-stable tumors were much less responsive. With microsatellite instability routinely tested by most centers, studies that include larger cohorts are required to study the predictive role of PD-1/PD-L1 expression in microsatellite instability–high CRC, to assess which immunohistochemistry antibodies to use, to refine the scoring criteria, and to critically analyze the interpretation pitfalls.

scholarly journals The Role of Immunotherapy in the Treatment of Adrenocortical Carcinoma

Biomedicines ◽  
2021 ◽  
Vol 9 (2) ◽  
pp. 98
Author(s):  
Izabela Karwacka ◽  
Łukasz Obołończyk ◽  
Sonia Kaniuka-Jakubowska ◽  
Krzysztof Sworczak
Keyword(s):  
Immune Checkpoint ◽  
Adrenocortical Carcinoma ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Treatment Options ◽  
Acquired Resistance ◽  
Distant Metastases ◽  
Immune Checkpoints ◽  
High Tendency

Adrenocortical carcinoma (ACC) is a rare epithelial neoplasm, with a high tendency for local invasion and distant metastases, with limited treatment options. Surgical treatment is the method of choice. For decades, the mainstay of pharmacological treatment has been the adrenolytic drug mitotane, in combination with chemotherapy. Immunotherapy is the latest revolution in cancer therapy, however preliminary data with single immune checkpoint inhibitors showed a modest activity in ACC patients. The anti-neoplastic activity of immune checkpoint inhibitors such as anti-cytotoxic-T-lymphocyte-associated-antigen 4 (anti-CTLA-4), anti-programmed death-1 (anti-PD-1), and anti-PD-ligand-1 (PD-L1) antibodies in different solid tumors has aroused interest to explore the potential therapeutic effect in ACC as well. Multiple ongoing clinical trials are currently evaluating the role of immune checkpoint inhibitors in ACC (pembrolizumab, combination pembrolizumab and relacorilant, nivolumab, combination nivolumab and ipilimumab). The primary and acquired resistance to immunotherapy continue to counter treatment efficacy. Therefore, attempts are made to combine therapy: anti-PD-1 antibody and anti-CTLA-4 antibody, anti-PD-1 antibody and antagonist of the glucocorticoid receptor. The inhibitors of immune checkpoints would benefit patients with antitumor immunity activated by radiotherapy. Immunotherapy is well tolerated by patients; the most frequently observed side effects are mild. The most common adverse effects of immunotherapy are skin and gastrointestinal disorders. The most common endocrinopathy during anti-CTLA treatment is pituitary inflammation and thyroid disorders.

scholarly journals At the Cutting Edge against Cancer: A Perspective on Immunoproteasome and Immune Checkpoints Modulation as a Potential Therapeutic Intervention

Cancers ◽  
2021 ◽  
Vol 13 (19) ◽  
pp. 4852
Author(s):  
Grazia R. Tundo ◽  
Diego Sbardella ◽  
Francesco Oddone ◽  
Anna A. Kudriaeva ◽  
Pedro M. Lacal ◽  
...  
Keyword(s):  
Antigen Processing ◽  
Checkpoint Inhibitors ◽  
Immune Checkpoints ◽  
Antigenic Peptides ◽  
Class I Mhc ◽  
Mhc Molecules ◽  
Promising Area ◽  
Potential Therapeutic Intervention ◽  
Antigen Repertoire

Immunoproteasome is a noncanonical form of proteasome with enzymological properties optimized for the generation of antigenic peptides presented in complex with class I MHC molecules. This enzymatic property makes the modulation of its activity a promising area of research. Nevertheless, immunotherapy has emerged as a front-line treatment of advanced/metastatic tumors providing outstanding improvement of life expectancy, even though not all patients achieve a long-lasting clinical benefit. To enhance the efficacy of the currently available immunotherapies and enable the development of new strategies, a broader knowledge of the dynamics of antigen repertoire processing by cancer cells is needed. Therefore, a better understanding of the role of immunoproteasome in antigen processing and of the therapeutic implication of its modulation is mandatory. Studies on the potential crosstalk between proteasome modulators and immune checkpoint inhibitors could provide novel perspectives and an unexplored treatment option for a variety of cancers.

scholarly journals NLRP3 Promotes Immune Escape by Regulating Immune Checkpoints: A Pan-cancer Analysis

2021 ◽  
Author(s):  
Yue Ding ◽  
Yilin Yan ◽  
Yihui Dong ◽  
Jingyuan Xu ◽  
Wei Su ◽  
...  
Keyword(s):  
Mononuclear Cells ◽  
Immune Escape ◽  
Checkpoint Inhibitors ◽  
Immune Checkpoints ◽  
Peripheral Blood Mononuclear ◽  
Intestinal Microbes ◽  
Tumor Mutational Burden ◽  
Liver Hepatocellular Carcinoma ◽  
Pan Cancer

Abstract NLRP3 plays a pathogenic role in tumorigenesis by regulating innate and acquired immunity, apoptosis, differentiation, and intestinal microbes in tumors. In different tumors, NLRP3 plays different roles, and its mechanism is complex. Our research aimed to comprehensively investigated the role of NLRP3 in pan-cancers based on multi-omics data in the TCGA database. We found the expression of NLRP3 was changed in tumors compared with paired non-tumor specimens. Most types of tumors showed increased expression of NLRP3. Among them, the overexpressed NLRP3 in liver hepatocellular carcinoma (LIHC) and ovarian cancer (OV) indicated worse overall survival (OS). Further analysis also confirmed overexpressed NLRP3 in colon cancer (COAD) indicated a high probability of microsatellite instability (MSI) and low tumor mutational burden (TMB), which indicated a better response to immune checkpoint inhibitors (ICIs). We also analyzed the association between NLRP3, immune infiltration, and immune checkpoints. Interestingly, overexpression of NLRP3 was closely related to high infiltration of immune cells (T cells, B cells, etc.) and overexpressed immune checkpoints (PD-1, PD-L1, LAG3, etc.). These results demonstrated NLRP3 promoted immune escape in cancers. Finally, we investigated the expression of various immune checkpoints by treating NLRP3 inhibitor MCC950 during the co-culture of peripheral blood mononuclear cells (PBMC) and LIHC cell line Hep3B. We found MCC950 significantly repressed the expression of PD-L1 and LAG3, and promoted the apoptosis rate of Hep3B. In conclusion, our research comprehensive demonstrated the role of NLRP3 in pan-cancer, especially in LIHC. We confirmed inhibition of NLRP3 promoting the immune killing effect to cancer cells by repressing the expression of immune checkpoints.

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