Practical cardiovascular imaging approach to diagnose immune checkpoint inhibitor myocarditis

2020 ◽  
Author(s):  
Lavanya Kondapalli ◽  
Theresa Medina ◽  
Daniel W Groves
Keyword(s):  
Cell Death ◽  
Programmed Cell Death ◽  
Immune Checkpoint ◽  
Kinase Inhibitors ◽  
Cytotoxic T Lymphocyte ◽  
Checkpoint Inhibitor ◽  
Checkpoint Inhibitors ◽  
Cancer Subtypes ◽  
Programmed Cell Death 1 ◽  
New Strategy

Abstract Immuno-oncology employs various therapeutic strategies that harness a patient’s own immune system to fight disease and has been a promising new strategy for cancer therapy over the last decade. Immune checkpoint inhibitors (ICI), are monoclonal antibodies, that increase antitumor immunity by blocking intrinsic down-regulators of immunity, such as cytotoxic T-lymphocyte antigen 4 (CTLA-4) and programmed cell death 1 (PD-1) or its ligand, programmed cell death ligand 1 (PD-L1). Seven ICIs are currently approved by the Food and Drug Administration and have increased the overall survival for patients with various cancer subtypes. These are used either as single agents or in combination with other checkpoint inhibitors, small molecular kinase inhibitors or cytotoxic chemotherapies. There are also many other immune modifying agents including other checkpoint inhibitor antibodies that are under investigation in clinical trials.

scholarly journals Insights into Potential Pathogenesis and Treatment Options for Immune-Checkpoint Inhibitor-Related Pneumonitis

Biomedicines ◽  
2021 ◽  
Vol 9 (10) ◽  
pp. 1484
Author(s):  
Hiroyuki Ando ◽  
Kunihiro Suzuki ◽  
Toyoshi Yanagihara
Keyword(s):  
Cell Death ◽  
Programmed Cell Death ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitor ◽  
Cytotoxic T Lymphocyte ◽  
Checkpoint Inhibitors ◽  
Treatment Options ◽  
Frequent Adverse Event ◽  
Programmed Cell Death 1 ◽  
New Treatment

Immune-checkpoint inhibitors (ICIs) targeting cytotoxic T-lymphocyte antigen 4 (CTLA-4), programmed cell death-1 (PD-1), and programmed cell death-1-ligand 1 (PD-L1) have become new treatment options for various malignancies. ICIs bind to immune-checkpoint inhibitory receptors or to the foregoing ligands and block inhibitory signals to release the brakes on the immune system, thereby enhancing immune anti-tumor responses. On the other hand, unlike conventional chemotherapies, ICIs can cause specific side effects, called immune-related adverse events (irAEs). These toxicities may affect various organs, including the lungs. ICI-related pneumonitis (ICI-pneumonitis) is not the most frequent adverse event, but it is serious and can be fatal. In this review, we summarize recent findings regarding ICI-pneumonitis, with a focus on potential pathogenesis and treatment.

scholarly journals Tracers for non-invasive radionuclide imaging of immune checkpoint expression in cancer

2019 ◽  
Vol 4 (1) ◽  
Author(s):  
Peter Wierstra ◽  
Gerwin Sandker ◽  
Erik Aarntzen ◽  
Martin Gotthardt ◽  
Gosse Adema ◽  
...  
Keyword(s):  
Cell Death ◽  
Molecular Imaging ◽  
Programmed Cell Death ◽  
Immune Checkpoint ◽  
Cytotoxic T Lymphocyte ◽  
Checkpoint Inhibitors ◽  
Immunohistochemical Analysis ◽  
Non Invasive ◽  
Programmed Cell Death 1 ◽  
Immunotherapy Target

Abstract Immunotherapy with checkpoint inhibitors demonstrates impressive improvements in the treatment of several types of cancer. Unfortunately, not all patients respond to therapy while severe immune-related adverse effects are prevalent. Currently, patient stratification is based on immunotherapy marker expression through immunohistochemical analysis on biopsied material. However, expression can be heterogeneous within and between tumor lesions, amplifying the sampling limitations of biopsies. Analysis of immunotherapy target expression by non-invasive quantitative molecular imaging with PET or SPECT may overcome this issue. In this review, an overview of tracers that have been developed for preclinical and clinical imaging of key immunotherapy targets, such as programmed cell death-1, programmed cell death ligand-1, IDO1 and cytotoxic T lymphocyte-associated antigen-4 is presented. We discuss important aspects to consider when developing such tracers and outline the future perspectives of molecular imaging of immunotherapy markers. Graphical abstract Current techniques in immune checkpoint imaging and its potential for future applications

scholarly journals Immune Checkpoint Inhibitor-Associated Colitis: From Mechanism to Management

2021 ◽  
Vol 12 ◽  
Author(s):  
Liansha Tang ◽  
Jialing Wang ◽  
Nan Lin ◽  
Yuwen Zhou ◽  
Wenbo He ◽  
...  
Keyword(s):  
Cell Death ◽  
Programmed Cell Death ◽  
Immune Checkpoint ◽  
Cytotoxic T Lymphocyte ◽  
Checkpoint Inhibitor ◽  
Checkpoint Inhibitors ◽  
Deep Understanding ◽  
Specific Pattern ◽  
The Body ◽  
Future Research

Immune checkpoint inhibitors (ICIs), as one of the innovative types of immunotherapies, including programmed cell death-1 (PD-1), programmed cell death-ligand 1 (PD-L1), and cytotoxic T lymphocyte antigen 4 (CTLA-4) inhibitors, have obtained unprecedented benefit in multiple malignancies. However, the immune response activation in the body organs could arise immune-related adverse events (irAEs). Checkpoint inhibitor colitis (CIC) is the most widely reported irAEs. However, some obscure problems, such as the mechanism concerning gut microbiota, the confusing differential diagnosis with inflammatory bowel disease (IBD), the optimal steroid schedule, the reintroduction of ICIs, and the controversial prognosis features, influence the deep understanding and precise diagnosis and management of CIC. Herein, we based on these problems and comprehensively summarized the relevant studies of CIC in patients with NSCLC, further discussing the future research direction of this specific pattern of irAEs.

scholarly journals Management of Hematologic Adverse Events Associated With Immune Checkpoint Inhibitors

2021 ◽  
Vol 12 (4) ◽  
Author(s):  
Barbara Barnes Rogers, CRNP, MN, AOCN, ANP-BC ◽  
Carolyn Zawislak, MPAS, PA-C ◽  
Victoria Wong, PA-C
Keyword(s):  
Cell Death ◽  
Programmed Cell Death ◽  
Adverse Events ◽  
Immune Checkpoint ◽  
Blood Cells ◽  
Immune Checkpoint Inhibitors ◽  
Cytotoxic T Lymphocyte ◽  
Checkpoint Inhibitors ◽  
White Blood Cells ◽  
Activated T Cells

Immune checkpoint inhibitors target suppressor receptors, including cytotoxic T-lymphocyte–associated antigen 4 (CTLA-4), programmed cell death protein 1 (PD-1), and programmed cell death ligand 1 (PD-L1). The activated T cells are not antigen specific; therefore, the blockade of the immune checkpoint may result in the development of autoimmune adverse events. The most common immune-related adverse events (irAEs) are rash, colitis, and endocrinopathies. However, irAEs that affect the hematologic system are rare and can affect red blood cells (e.g., autoimmune hemolytic anemia), white blood cells, and platelets (e.g., immune thrombocytopenia). Usually one cell line is affected; however, in some cases, multiple cell lines can be affected. Other changes in the hematologic system can also be affected (e.g., cryoglobulinemia, cytokine release syndrome). Due to the rarity and lack of recognition of these AEs, the timing, spectrum of events, and clinical presentation are poorly understood. Management of hematologic irAEs usually involves the use of steroids; however, other agents (e.g., IVIG, cyclosporine, rituximab) or procedures (e.g., plasma exchange, transfusions) can also be used.

scholarly journals A Case of Poorly Differentiated Hepatocellular Carcinoma, Lymphocyte-rich.

2021 ◽  
Author(s):  
Ginji Omori ◽  
Takahiro Osuga ◽  
Koji Miyanishi ◽  
Kota Hamaguchi ◽  
Shingo Tanaka ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Death ◽  
Programmed Cell Death ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitor ◽  
Programmed Cell Death 1 ◽  
Poorly Differentiated ◽  
Inhibitor Treatment

A 70-year-old woman was diagnosed poorly differentiated hepatocellular carcinoma (HCC), lymphocyte rich. In this case, programmed cell death 1 expression was observed. Immune checkpoint inhibitor treatment may be effective in such cases, although there have been no reports of their use for poorly differentiated HCC, lymphocyte-rich.

scholarly journals The Tumor Microenvironment in SCC: Mechanisms and Therapeutic Opportunities

2021 ◽  
Vol 9 ◽  
Author(s):  
Nádia Ghinelli Amôr ◽  
Paulo Sérgio da Silva Santos ◽  
Ana Paula Campanelli
Keyword(s):  
Cell Death ◽  
Monoclonal Antibodies ◽  
Tumor Microenvironment ◽  
Programmed Cell Death ◽  
T Cell Activation ◽  
Immune Checkpoint ◽  
Cell Activation ◽  
Cytotoxic T Lymphocyte ◽  
Checkpoint Inhibitors ◽  
Immune Checkpoint Molecules

Squamous cell carcinoma (SCC) is the second most common skin cancer worldwide and, despite the relatively easy visualization of the tumor in the clinic, a sizeable number of SCC patients are diagnosed at advanced stages with local invasion and distant metastatic lesions. In the last decade, immunotherapy has emerged as the fourth pillar in cancer therapy via the targeting of immune checkpoint molecules such as programmed cell-death protein-1 (PD-1), programmed cell death ligand-1 (PD-L1), and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4). FDA-approved monoclonal antibodies directed against these immune targets have provide survival benefit in a growing list of cancer types. Currently, there are two immunotherapy drugs available for cutaneous SCC: cemiplimab and pembrolizumab; both monoclonal antibodies (mAb) that block PD-1 thereby promoting T-cell activation and/or function. However, the success rate of these checkpoint inhibitors currently remains around 50%, which means that half of the patients with advanced SCC experience no benefit from this treatment. This review will highlight the mechanisms by which the immune checkpoint molecules regulate the tumor microenvironment (TME), as well as the ongoing clinical trials that are employing single or combinatory therapeutic approaches for SCC immunotherapy. We also discuss the regulation of additional pathways that might promote superior therapeutic efficacy, and consequently provide increased survival for those patients that do not benefit from the current checkpoint inhibitor therapies.

scholarly journals Next generation of immune checkpoint inhibitors and beyond

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Julian A. Marin-Acevedo ◽  
ErinMarie O. Kimbrough ◽  
Yanyan Lou
Keyword(s):  
Cell Death ◽  
Immune System ◽  
Programmed Cell Death ◽  
Immune Checkpoint ◽  
Cytotoxic T Lymphocyte ◽  
Checkpoint Inhibitors ◽  
Death Receptor ◽  
Immune Checkpoints ◽  
Host Immune System ◽  
Immune Recognition

AbstractThe immune system is the core defense against cancer development and progression. Failure of the immune system to recognize and eliminate malignant cells plays an important role in the pathogenesis of cancer. Tumor cells evade immune recognition, in part, due to the immunosuppressive features of the tumor microenvironment. Immunotherapy augments the host immune system to generate an antitumor effect. Immune checkpoints are pathways with inhibitory or stimulatory features that maintain self-tolerance and assist with immune response. The most well-described checkpoints are inhibitory in nature and include the cytotoxic T lymphocyte-associated molecule-4 (CTLA-4), programmed cell death receptor-1 (PD-1), and programmed cell death ligand-1 (PD-L1). Molecules that block these pathways to enhance the host immunologic activity against tumors have been developed and become standard of care in the treatment of many malignancies. Only a small percentage of patients have meaningful responses to these treatments, however. New pathways and molecules are being explored in an attempt to improve responses and application of immune checkpoint inhibition therapy. In this review, we aim to elucidate these novel immune inhibitory pathways, potential therapeutic molecules that are under development, and outline particular advantages and challenges with the use of each one of them.

scholarly journals PD-L1, an Important Immune Checkpoint Regulator, Is Suppressed by miR-34a in Head and Neck Squamous Cell Carcinoma

2020 ◽  
Author(s):  
Kenjiro Higashi ◽  
Takenori Ogawa ◽  
Yuriko Saiki ◽  
Tomohiko Ishikawa ◽  
Yuta Kobayashi ◽  
...  
Keyword(s):  
Cell Death ◽  
Programmed Cell Death ◽  
Head And Neck ◽  
Cell Lines ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Expression Levels ◽  
Programmed Cell Death 1 ◽  
Hnscc Cell

Abstract Background: Key molecules regulating the immune checkpoint have shed light on the efforts to control several cancers. Recently, immune checkpoint inhibitors for cancer therapy such as antibodies against programmed cell death 1 (PD-1), programmed cell death 1 ligand 1 (PD-L1), and cytotoxic T-lymphocyte associated protein 4 (CTLA4) have been developed. In head and neck squamous cell carcinomas (HNSCCs), such immune checkpoint inhibitors have come into clinical use and are expected to improve patients’ prognoses. Recently, miR-34a has been shown to be a downstream micro RNA of TP53 that regulates PD-L1 in several types of cancer. To reveal the correlations between miR-34a and PD-L1 in HNSCCs in terms of clinical significance, we analyzed 19 HNSCC cell lines.Methods: We measured the expression levels of miR-34a and PD-L1 in 10 HNSCC cell lines as well as in 9 of their derived acquired cisplatin (CDDP) resistant cell lines by qRT-PCR and Western blotting. Results were further analyzed by their TP53 statuses. We also investigated the changes in PD-L1 expression levels after miR-34a precursor- or inhibitor-mediated forced expression or suppression in HNSCC cell lines. Results: We observed inverse correlations between both mRNA and protein expression levels of miR-34a and PD-L1. No significant differences in miR-34a levels were observed with regard to TP53 status. Forced expression of miR-34a decreased PD-L1 expression, and suppression of miR-34a increased PD-L1 expression. Conclusion: Our present results suggest that miR-34a negatively regulates PD-L1 expression, possibly in a TP53 independent manner in HNSCC.

Immune checkpoint inhibitor-induced gastrointestinal and hepatic injury: pathologists’ perspective

2018 ◽  
Vol 71 (8) ◽  
pp. 665-671 ◽  
Author(s):  
Dipti M Karamchandani ◽  
Runjan Chetty
Keyword(s):  
Cell Death ◽  
Programmed Cell Death ◽  
Immune Checkpoint ◽  
Cytotoxic T Lymphocyte ◽  
Checkpoint Inhibitors ◽  
Survival Rates ◽  
Immune Mediated ◽  
Self Tolerance ◽  
Novel Drugs ◽  
Cell Death Protein

Immune checkpoint inhibitors (CPIs) are a relatively new class of ‘miracle’ dugs that have revolutionised the treatment and prognosis of some advanced-stage malignancies, and have increased the survival rates significantly. This class of drugs includes cytotoxic T lymphocyte antigen-4 inhibitors such as ipilimumab; programmed cell death protein-1 inhibitors such as nivolumab, pembrolizumab and avelumab; and programmed cell death protein ligand-1 inhibitors such as atezolizumab. These drugs stimulate the immune system by blocking the coinhibitory receptors on the T cells and lead to antitumoural response. However, a flip side of these novel drugs is immune-related adverse events (irAEs), secondary to immune-mediated process due to disrupted self-tolerance. The irAEs in the gastrointestinal (GI) tract/liver may result in diarrhoea, colitis or hepatitis. An accurate diagnosis of CPI-induced colitis and/or hepatitis is essential for optimal patient management. As we anticipate greater use of these drugs in the future given the significant clinical response, pathologists need to be aware of the spectrum of histological findings that may be encountered in GI and/or liver biopsies received from these patients, as well as differentiate them from its histopathological mimics. This present review discusses the clinical features, detailed histopathological features, management and the differential diagnosis of the luminal GI and hepatic irAEs that may be encountered secondary to CPI therapy.

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