Cancers

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17 pages, 3245 KiB

Open AccessArticle

Extracellular Vesicle-Derived Protein File from Peripheral Blood Predicts Immune-Related Adverse Events in Gastric Cancer Patients Receiving Immunotherapy

by Fangli Jiang, Zhening Zhang, Xiaoyi Chong, Lin Shen, Meng Fan, Xuan Liu, Jin An, Zhi Peng and Cheng Zhang

Cancers 2022, 14(17), 4167; https://doi.org/10.3390/cancers14174167 - 28 Aug 2022

Cited by 8 | Viewed by 2163

Abstract

Immune checkpoint inhibitors (ICIs) initiate a new stage for gastric cancer (GC) therapeutics, and plenty of patients have already benefited from ICIs. Liquid biopsy promotes the development of precision medicine of GC. However, due to the lack of precision biomarkers of immune-related adverse [...] Read more.

Immune checkpoint inhibitors (ICIs) initiate a new stage for gastric cancer (GC) therapeutics, and plenty of patients have already benefited from ICIs. Liquid biopsy promotes the development of precision medicine of GC. However, due to the lack of precision biomarkers of immune-related adverse events (irAEs), the safety of ICIs-treated GC patients cannot be guaranteed. In our study, GC patients treated with ICIs were included for investigating the correlation between irAEs of ICIs and corresponding outcomes. We also explored the potential of biomarkers of irAEs via EV-derived proteins. Dynamic plasma was taken from 102 ICIs-treated GC patients generated retrospectively or prospectively, who were divided into discovery and validating cohorts. Plasma EV-derived protein profiles were described, and two EV-proteins, inducible T-cell co-stimulator (EV-ICOS) and indoleamine 2,3-dioxygenase 1(EV-IDO1), from 42 vital proteins were screened to predict the prognosis of ICIs with irAEs. Our work is the first to propose that EV-proteins can predict ICIs-corresponding irAEs, which can be conducive to the diagnosis and treatment of GC patients, and to facilitate the screening of beneficiaries. Full article

(This article belongs to the Special Issue Cancer Immunotherapy and Immune-Related Adverse Events)

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15 pages, 1410 KiB

Open AccessArticle

Peripheral Blood Biomarkers Predictive of Efficacy Outcome and Immune-Related Adverse Events in Advanced Gastrointestinal Cancers Treated with Checkpoint Inhibitors

by Zhening Zhang, Tong Xie, Changsong Qi, Xiaotian Zhang, Lin Shen and Zhi Peng

Cancers 2022, 14(15), 3736; https://doi.org/10.3390/cancers14153736 - 31 Jul 2022

Cited by 8 | Viewed by 2294

Abstract

Background: Gastrointestinal cancers constitute a major burden of global cancer mortalities. In recent years, the advent of immune checkpoint inhibitors has greatly improved the survival of patients with advanced gastrointestinal cancers, while predictive biomarkers of treatment efficacy and toxicities are still unmet demands. [...] Read more.

Background: Gastrointestinal cancers constitute a major burden of global cancer mortalities. In recent years, the advent of immune checkpoint inhibitors has greatly improved the survival of patients with advanced gastrointestinal cancers, while predictive biomarkers of treatment efficacy and toxicities are still unmet demands. Methods: In our retrospective study, patients with advanced gastrointestinal cancers who received single or double immune checkpoint inhibitors in the Department of Gastrointestinal Oncology in Peking University Cancer Hospital between July 2016 and February 2022 were enrolled. Records of clinicopathological information, survival parameters, safety data, and baseline and posttreatment peripheral blood constituents were retrieved. Cox regression analysis and logistic regression analysis were performed to identify the predictive factors of treatment outcomes and immune-related adverse events. Results: We demonstrated that early treatment lines, the presence of immune-related adverse events, and a lower C2 neutrophil-to-lymphocyte ratio were independent factors predicting a superior objective response rate and progression-free survival in patients treated with immunotherapy. Lower ECOG PS, higher baseline albumin, and lower C2 neutrophil-to-lymphocyte ratios were independent risk factors for the onset of immune-related adverse events. Patients who succumbed to immune-related adverse events during immunotherapy presented better survival. Conclusion: Our results indicate that peripheral blood markers have potential for predicting treatment outcomes and immune-related adverse events in patients with advanced gastrointestinal cancer. Prospective validations are warranted. Full article

(This article belongs to the Special Issue Cancer Immunotherapy and Immune-Related Adverse Events)

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13 pages, 1123 KiB

Open AccessArticle

Association of Rare Immune-Related Adverse Events to Survival in Advanced Cancer Patients Treated with Immune Checkpoint Inhibitors: A Real-World Single-Center Cohort Study

by Saara Kuusisalo, Jussi P. Koivunen and Sanna Iivanainen

Cancers 2022, 14(9), 2276; https://doi.org/10.3390/cancers14092276 - 3 May 2022

Cited by 3 | Viewed by 2707

Abstract

Immune checkpoint inhibitors (ICIs) are associated with immune-related (ir) adverse events (AEs) resembling autoimmune diseases. In this retrospective cohort study of patients (pts) treated with ICIs at Oulu University Hospital from 2014–2020, we analysed the spectrum of severe irAEs and their prognostic nature, [...] Read more.

Immune checkpoint inhibitors (ICIs) are associated with immune-related (ir) adverse events (AEs) resembling autoimmune diseases. In this retrospective cohort study of patients (pts) treated with ICIs at Oulu University Hospital from 2014–2020, we analysed the spectrum of severe irAEs and their prognostic nature, focusing on rare irAEs. Pts (n = 173) with lung cancer (n = 76, 43.9%), melanoma (n = 56, 32.4%), renal and bladder cancers (n = 34, 19.7%), head and neck cancers (n = 4, 2.3%), SCC (n = 2, 1.2%), and CRC (n = 1, 0.6%) receiving single anti-PD-(L)1 (n = 160) or combination (ICI-ICI n = 9, ICI-chemotherapy n = 4) therapy were included. The survival analysis focused on single anti-PD-(L)1-treated patients with melanoma, lung cancer, and renal and bladder cancers (n = 142). Grade ≥ 3 irAEs of multiple aetiology occurred in 29 patients treated with single-PD-L1 therapy (20.4%), which was associated with improved progression-free survival (PFS) (HR 0.50, CI 0.31–0.78) but not overall survival (OS) (HR 0.88, CI 0.52–1.50). Rare grade ≥ 3 events occurred in 10 (7.0%) pts with no association with PFS (HR 0.90, CI 0.42–1.94). Hence, the presence of rare grade ≥ 3 irAEs was associated with a tendency for inferior OS (HR 1.44, CI 0.66–3.11). Pts with rare grade ≥ 3 irAEs had inferior OS, possibly reflecting the delay in diagnostic workflow and the treatment of irAEs. One explanation for the high incidence of irAEs could be the Finnish population-based genetic variation affecting the immune system. Full article

(This article belongs to the Special Issue Cancer Immunotherapy and Immune-Related Adverse Events)

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12 pages, 709 KiB

Open AccessArticle

Association between Body Mass Index and Immune-Related Adverse Events (irAEs) among Advanced-Stage Cancer Patients Receiving Immune Checkpoint Inhibitors: A Pan-Cancer Analysis

by Dongyu Zhang, Neil J. Shah, Michael Cook, Matthew Blackburn, Michael T. Serzan, Shailesh Advani, Arnold L. Potosky, Subha Madhavan, Anas Belouali, Michael B. Atkins and Dejana Braithwaite

Cancers 2021, 13(23), 6109; https://doi.org/10.3390/cancers13236109 - 3 Dec 2021

Cited by 13 | Viewed by 2773 | Correction

Abstract

Evidence regarding the association between body mass index (BMI) and immune-related adverse events (irAEs) among cancer patients receiving immune checkpoint inhibitors (ICIs) is limited. Here, we use cross-sectional hospital-based data to explore their relationship. Pre-treatment BMI was treated as an ordinal variable (<25, [...] Read more.

Evidence regarding the association between body mass index (BMI) and immune-related adverse events (irAEs) among cancer patients receiving immune checkpoint inhibitors (ICIs) is limited. Here, we use cross-sectional hospital-based data to explore their relationship. Pre-treatment BMI was treated as an ordinal variable (<25, 25 to ≤30, ≥30 kg/m²). The outcome of interest was irAEs after ICI initiation. A multivariable logistic regression model estimated the adjusted odds ratio (aOR) and 95% confidence interval (CI) of BMI. A total of 684 patients with stage III or IV cancer were included in the study (lung: 269, melanoma: 204, other: 211). The mean age at the first dose of ICI was 64.1 years (SD = 13.5), 394 patients (57.6%) were male, and over one-third (N = 260, 38.0%) were non-White. Overall, 52.9% of patients had BMI ≥ 25 kg/m² (25 to ≤30: 217, ≥30: 145) and 288 (42.1%) had irAEs after ICI treatment. Patients with higher BMI tended to have a higher rate of irAEs (<25: 35.7%, 25 to ≤30: 47.0%, ≥30: 49.0%). The multivariable logistic regression yielded consistent results (BMI ≥ 30 vs. BMI < 25: aOR = 1.47, 95% CI = 0.96–2.23; 25 ≤ BMI < 30 vs. BMI < 25: aOR = 1.46, 95% CI = 1.02–2.11, p-trend = 0.04). In conclusion, among patients with advanced cancer receiving ICIs, the rate of irAEs appears to be higher among those with higher BMI. Full article

(This article belongs to the Special Issue Cancer Immunotherapy and Immune-Related Adverse Events)

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14 pages, 3437 KiB

Open AccessArticle

CD18 Antibody Application Blocks Unwanted Off-Target T Cell Activation Caused by Bispecific Antibodies

by Joseph Kauer, Fabian Vogt, Ilona Hagelstein, Sebastian Hörner, Melanie Märklin, Stefanie Maurer, Helmut R. Salih, Gundram Jung and Latifa Zekri

Cancers 2021, 13(18), 4596; https://doi.org/10.3390/cancers13184596 - 13 Sep 2021

Cited by 1 | Viewed by 3938

Abstract

T cell-recruiting bispecific antibodies (bsAbs) are successfully used for the treatment of cancer. However, effective treatment with bsAbs is so far hampered by severe side effects, i.e., potentially life-threatening cytokine release syndrome. Off-target T cell activation due to binding of bispecific CD3 antibodies [...] Read more.

T cell-recruiting bispecific antibodies (bsAbs) are successfully used for the treatment of cancer. However, effective treatment with bsAbs is so far hampered by severe side effects, i.e., potentially life-threatening cytokine release syndrome. Off-target T cell activation due to binding of bispecific CD3 antibodies to T cells in the absence of target cells may contribute to excessive cytokine release. We report here, in an in vitro setting, that off-target T cell activation is induced by bsAbs with high CD3 binding affinity and increased by endothelial- or lymphoid cells that act as stimulating bystander cells. Blocking antibodies directed against the adhesion molecules CD18/CD54 or CD2/CD58 markedly reduced this type of off-target T cell activation. CD18 blockade—in contrast to CD2—did not affect the therapeutic activity of various bsAbs. Since CD18 antibodies have been shown to be safely applicable in patients, blockade of this integrin holds promise as a potential target for the prevention of unwanted off-target T cell activation and allows the application of truly effective bsAb doses. Full article

(This article belongs to the Special Issue Cancer Immunotherapy and Immune-Related Adverse Events)

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15 pages, 1982 KiB

Open AccessArticle

Vaccination against PD-L1 with IO103 a Novel Immune Modulatory Vaccine in Basal Cell Carcinoma: A Phase IIa Study

by Nicolai Grønne Jørgensen, Jeanette Kaae, Jacob Handlos Grauslund, Özcan Met, Signe Ledou Nielsen, Ayako Wakatsuki Pedersen, Inge Marie Svane, Eva Ehrnrooth, Mads Hald Andersen, Claus Zachariae and Lone Skov

Cancers 2021, 13(4), 911; https://doi.org/10.3390/cancers13040911 - 22 Feb 2021

Cited by 10 | Viewed by 2829

Abstract

Antitumor activity of immune checkpoint blocking antibodies against programmed death 1 (PD-1) in basal cell carcinoma (BCC) has been described. IO103 is a peptide vaccine against the major PD-1 ligand PD-L1. A phase IIa study of vaccination with IO103 and Montanide adjuvant was [...] Read more.

Antitumor activity of immune checkpoint blocking antibodies against programmed death 1 (PD-1) in basal cell carcinoma (BCC) has been described. IO103 is a peptide vaccine against the major PD-1 ligand PD-L1. A phase IIa study of vaccination with IO103 and Montanide adjuvant was conducted in patients with resectable BCC (NCT03714529). Vaccinations were given six times every 2 weeks (q2w), followed by three vaccines q4w in responders. Primary endpoints were clinical responses of target tumors, change in target tumor size and immune responses to the vaccine. Secondary endpoint was safety. One tumor per patient was designated target tumor and biopsied twice during the course of vaccination. Synchronous non-target BCCs were not biopsied during vaccinations. Ten patients were vaccinated (six patients received six vaccinations and four patients received nine vaccinations). A partial response (PR) was seen in two target tumors. Two complete responses (CR) and one PR were observed in eight non-target tumors in four patients. No tumors progressed. Related adverse events were grade 1 and reversible. Immune responses against IO103 were induced in blood samples from nine of ten and skin-infiltrating lymphocytes from five of the nine patients. The regressions seen in non-target tumors suggest that IO103 may be effective against a subtype of BCC. Full article

(This article belongs to the Special Issue Cancer Immunotherapy and Immune-Related Adverse Events)

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Review

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24 pages, 1725 KiB

Open AccessReview

Current Progress of CAR-NK Therapy in Cancer Treatment

by Zhaojun Pang, Zhongyi Wang, Fengqi Li, Chunjing Feng and Xin Mu

Cancers 2022, 14(17), 4318; https://doi.org/10.3390/cancers14174318 - 2 Sep 2022

Cited by 25 | Viewed by 5662

Abstract

CD8⁺ T cells and natural killer (NK) cells eliminate target cells through the release of lytic granules and Fas ligand (FasL)-induced target cell apoptosis. The introduction of chimeric antigen receptor (CAR) makes these two types of cells selective and effective in killing [...] Read more.

CD8⁺ T cells and natural killer (NK) cells eliminate target cells through the release of lytic granules and Fas ligand (FasL)-induced target cell apoptosis. The introduction of chimeric antigen receptor (CAR) makes these two types of cells selective and effective in killing cancer cells. The success of CAR-T therapy in the treatment of acute lymphoblastic leukemia (ALL) and other types of blood cancers proved that the immunotherapy is an effective approach in fighting against cancers, yet adverse effects, such as graft versus host disease (GvHD) and cytokine release syndrome (CRS), cannot be ignored for the CAR-T therapy. CAR-NK therapy, then, has its advantage in lacking these adverse effects and works as effective as CAR-T in terms of killing. Despite these, NK cells are known to be hard to transduce, expand in vitro, and sustain shorter in vivo comparing to infiltrated T cells. Moreover, CAR-NK therapy faces challenges as CAR-T therapy does, e.g., the time, the cost, and the potential biohazard due to the use of animal-derived products. Thus, enormous efforts are needed to develop safe, effective, and large-scalable protocols for obtaining CAR-NK cells. Here, we reviewed current progress of CAR-NK therapy, including its biological properties, CAR compositions, preparation of CAR-NK cells, and clinical progresses. We also discussed safety issues raised from genetic engineering. We hope this review is instructive to the research community and a broad range of readers. Full article

(This article belongs to the Special Issue Cancer Immunotherapy and Immune-Related Adverse Events)

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24 pages, 498 KiB

Open AccessReview

Adverse Renal Effects of Anticancer Immunotherapy: A Review

by Maciej Borówka, Stanisław Łącki-Zynzeling, Michał Nicze, Sylwia Kozak and Jerzy Chudek

Cancers 2022, 14(17), 4086; https://doi.org/10.3390/cancers14174086 - 23 Aug 2022

Cited by 6 | Viewed by 4081

Abstract

Modern oncological therapy utilizes various types of immunotherapy. Immune checkpoint inhibitors (ICIs), chimeric antigen receptor T cells (CAR-T) therapy, cancer vaccines, tumor-targeting monoclonal antibodies (TT-mAbs), bispecific antibodies and cytokine therapy improve patients’ outcomes. However, stimulation of the immune system, beneficial in terms of [...] Read more.

Modern oncological therapy utilizes various types of immunotherapy. Immune checkpoint inhibitors (ICIs), chimeric antigen receptor T cells (CAR-T) therapy, cancer vaccines, tumor-targeting monoclonal antibodies (TT-mAbs), bispecific antibodies and cytokine therapy improve patients’ outcomes. However, stimulation of the immune system, beneficial in terms of fighting against cancer, generates the risk of harm to other cells in a patient’s body. Kidney damage belongs to the relatively rare adverse events (AEs). Best described, but still, superficially, are renal AEs in patients treated with ICIs. International guidelines issued by the European Society for Medical Oncology (ESMO) and the American Society of Clinical Oncology (ASCO) cover the management of immune-related adverse events (irAEs) during ICI therapy. There are fewer data concerning real occurrence and possible presentations of renal adverse drug reactions of other immunotherapeutic methods. This implies the need for the collection of safety data during ongoing clinical trials and in the real-life world to characterize the hazard related to the use of new immunotherapies and management of irAEs. Full article

(This article belongs to the Special Issue Cancer Immunotherapy and Immune-Related Adverse Events)

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30 pages, 846 KiB

Open AccessReview

Comparative Analysis of Predictive Biomarkers for PD-1/PD-L1 Inhibitors in Cancers: Developments and Challenges

by Fang Yang, Jacqueline F. Wang, Yucai Wang, Baorui Liu and Julian R. Molina

Cancers 2022, 14(1), 109; https://doi.org/10.3390/cancers14010109 - 27 Dec 2021

Cited by 28 | Viewed by 4713

Abstract

Immune checkpoint inhibitors (ICIs) targeting programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) have dramatically changed the landscape of cancer therapy. Both remarkable and durable responses have been observed in patients with melanoma, non-small-cell lung cancer (NSCLC), and other malignancies. However, the [...] Read more.

Immune checkpoint inhibitors (ICIs) targeting programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) have dramatically changed the landscape of cancer therapy. Both remarkable and durable responses have been observed in patients with melanoma, non-small-cell lung cancer (NSCLC), and other malignancies. However, the PD-1/PD-L1 blockade has demonstrated meaningful clinical responses and benefits in only a subset of patients. In addition, several severe and life-threatening adverse events were observed in these patients. Therefore, the identification of predictive biomarkers is urgently needed to select patients who are more likely to benefit from ICI therapy. PD-L1 expression level is the most commonly used biomarker in clinical practice for PD-1/PD-L1 inhibitors. However, negative PD-L1 expression cannot reliably exclude a response to a PD-1/PD-L1 blockade. Other factors, such as tumor microenvironment and other tumor genomic signatures, appear to impact the response to ICIs. In this review, we examine emerging data for novel biomarkers that may have a predictive value for optimizing the benefit from anti-PD-1/PD-L1 immunotherapy. Full article

(This article belongs to the Special Issue Cancer Immunotherapy and Immune-Related Adverse Events)

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15 pages, 286 KiB

Open AccessReview

The Gut Microbiome and Cancer Immunotherapy: Can We Use the Gut Microbiome as a Predictive Biomarker for Clinical Response in Cancer Immunotherapy?

by Byeongsang Oh, Frances Boyle, Nick Pavlakis, Stephen Clarke, Thomas Eade, George Hruby, Gillian Lamoury, Susan Carroll, Marita Morgia, Andrew Kneebone, Mark Stevens, Wen Liu, Brian Corless, Mark Molloy, Benjamin Kong, Towia Libermann, David Rosenthal and Michael Back

Cancers 2021, 13(19), 4824; https://doi.org/10.3390/cancers13194824 - 27 Sep 2021

Cited by 33 | Viewed by 5378

Abstract

Background: Emerging evidence suggests that gut microbiota influences the clinical response to immunotherapy. This review of clinical studies examines the relationship between gut microbiota and immunotherapy outcomes. Method: A literature search was conducted in electronic databases Medline, PubMed and ScienceDirect, with searches for [...] Read more.

Background: Emerging evidence suggests that gut microbiota influences the clinical response to immunotherapy. This review of clinical studies examines the relationship between gut microbiota and immunotherapy outcomes. Method: A literature search was conducted in electronic databases Medline, PubMed and ScienceDirect, with searches for “cancer” and “immunotherapy/immune checkpoint inhibitor” and “microbiome/microbiota” and/or “fecal microbiome transplant FMT”. The relevant literature was selected for this article. Results: Ten studies examined patients diagnosed with advanced metastatic melanoma (n = 6), hepatocellular carcinoma (HCC) (n = 2), non-small cell lung carcinoma (NSCLC) (n = 1) and one study examined combination both NSCLC and renal cell carcinoma (RCC) (n = 1). These studies consistently reported that the gut microbiome profile prior to administering immune checkpoint inhibitors (ICIs) was related to clinical response as measured by progression-free survival (PFS) and overall survival (OS). Two studies reported that a low abundance of Bacteroidetes was associated with colitis. Two studies showed that patients with anti-PD-1 refractory metastatic melanoma experienced improved response rates and no added toxicity when receiving fecal microbiota transplant (FMT) from patients with anti-PD-1 responsive disease. Conclusions: Overall, significant differences in the diversity and composition of the gut microbiome were identified in ICIs responders and non-responders. Our findings provide new insights into the value of assessing the gut microbiome in immunotherapy. Further robust randomized controlled trials (RCTs) examining the modulatory effects of the gut microbiome and FMT on ICIs in patients not responding to immunotherapy are warranted. Full article

(This article belongs to the Special Issue Cancer Immunotherapy and Immune-Related Adverse Events)

22 pages, 963 KiB

Open AccessReview

Targeting Immune Modulators in Glioma While Avoiding Autoimmune Conditions

by Lynn Bitar, Ulrike Schumann, Renate König, Frauke Zipp and Mirko H. H. Schmidt

Cancers 2021, 13(14), 3524; https://doi.org/10.3390/cancers13143524 - 14 Jul 2021

Cited by 4 | Viewed by 3529

Abstract

Communication signals and signaling pathways are often studied in different physiological systems. However, it has become abundantly clear that the immune system is not self-regulated, but functions in close association with the nervous system. The neural–immune interface is complex; its balance determines cancer [...] Read more.

Communication signals and signaling pathways are often studied in different physiological systems. However, it has become abundantly clear that the immune system is not self-regulated, but functions in close association with the nervous system. The neural–immune interface is complex; its balance determines cancer progression, as well as autoimmune disorders. Immunotherapy remains a promising approach in the context of glioblastoma multiforme (GBM). The primary obstacle to finding effective therapies is the potent immunosuppression induced by GBM. Anti-inflammatory cytokines, induction of regulatory T cells, and the expression of immune checkpoint molecules are the key mediators for immunosuppression in the tumor microenvironment. Immune checkpoint molecules are ligand–receptor pairs that exert inhibitory or stimulatory effects on immune responses. In the past decade, they have been extensively studied in preclinical and clinical trials in diseases such as cancer or autoimmune diseases in which the immune system has failed to maintain homeostasis. In this review, we will discuss promising immune-modulatory targets that are in the focus of current clinical research in glioblastoma, but are also in the precarious position of potentially becoming starting points for the development of autoimmune diseases like multiple sclerosis. Full article

(This article belongs to the Special Issue Cancer Immunotherapy and Immune-Related Adverse Events)

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2 pages, 170 KiB

Open AccessCorrection

Correction: Zhang et al. Association between Body Mass Index and Immune-Related Adverse Events (irAEs) among Advanced-Stage Cancer Patients Receiving Immune Checkpoint Inhibitors: A Pan-Cancer Analysis. Cancers 2021, 13, 6109

by Dongyu Zhang, Neil J. Shah, Michael Cook, Matthew Blackburn, Michael T. Serzan, Shailesh Advani, Arnold L. Potosky, Subha Madhavan, Anas Belouali, Michael B. Atkins and Dejana Braithwaite

Cancers 2022, 14(18), 4525; https://doi.org/10.3390/cancers14184525 - 19 Sep 2022

Cited by 2 | Viewed by 1610

Abstract

Subha Madhavan (S.M.) and Anas Belouali (A.B.) were not included as authors in the published article [...] Full article

(This article belongs to the Special Issue Cancer Immunotherapy and Immune-Related Adverse Events)

24 pages, 1181 KiB

Open AccessSystematic Review

Cardiac Toxicity Associated with Immune Checkpoint Inhibitors: A Systematic Review

by Walid Shalata, Amjad Abu-salman, Rachel Steckbeck, Binil Mathew Jacob, Ismaell Massalha and Alexander Yakobson

Cancers 2021, 13(20), 5218; https://doi.org/10.3390/cancers13205218 - 18 Oct 2021

Cited by 71 | Viewed by 5446

Abstract

Immune checkpoint inhibitors are immune stimulatory drugs used to treat many types of cancer. These drugs are antibodies against inhibitory proteins, such as CTLA-4 and PD-1/PD-L1, that are expressed on immune cells. When bound, they allow for increased stimulation of T cells to [...] Read more.

Immune checkpoint inhibitors are immune stimulatory drugs used to treat many types of cancer. These drugs are antibodies against inhibitory proteins, such as CTLA-4 and PD-1/PD-L1, that are expressed on immune cells. When bound, they allow for increased stimulation of T cells to fight tumor cells. However, immune checkpoint inhibitors have several immune-related adverse effects. Many cases have come to light recently of cardiotoxicity as a result of treatment with these drugs. Cardiotoxicity from immune checkpoint inhibitors is unique due to its rarity and high mortality rate. Patients with this toxicity may present with myocarditis, pericarditis, Takotsubo cardiomyopathy, conduction disorders, and others within just a few weeks of starting immune checkpoint inhibitors. We present here a review of the current research on immune checkpoint inhibitors, their associated cardiotoxicities, the timing of presentation of these conditions, lab tests and histology for each condition, and finally the treatment of patients with cardiotoxicity. We observe a positive skew in the onset of presentation, which is significant for the treating physician. Full article

(This article belongs to the Special Issue Cancer Immunotherapy and Immune-Related Adverse Events)

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