Checkpoint inhibitor-induced fulminant myocarditis, complete atrioventricular block and myasthenia gravis—a case report

Hernández, Antonio Portolés; Clemente, M. Blanco; García, Daniel; Calvo, Rocío Velasco; García, Beatriz; Domínguez, Juan Francisco Oteo; Antón, Clara Salas; Garcia, M. Mendez; Cubero, Javier Segovia; Domínguez, Fernándo

doi:10.21037/cdt-21-147

Cited by 18 publications

(14 citation statements)

References 11 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Considering steroids as the main treatment for immune myocarditis, we also summarized new immune checkpoint inhibition into the biologic agent category in Table 2 , including six case-use reports of infliximab, one case of anti-thymocyte globulin (ATG), and one case of abatacept. Two studies reported nonsignificant improvement in symptoms related to myocarditis with infliximab ( 51 , 52 ), while three cases reported a worsening manifestation of symptoms related to myocarditis with infliximab ( 53 – 55 ), and another study reported the use of infliximab but not describing the results ( 26 ). One study found the use of ATG was suspended due to poor patient status ( 56 ), and another study reported the myocarditis symptoms were improved with the use of Abatacept ( 57 ).…”

Section: Discussionmentioning

confidence: 99%

Immune checkpoint inhibitor–associated myocarditis: a systematic analysis of case reports

Wang,

Zhao,

Zhang

et al. 2023

Front. Immunol.

View full text Add to dashboard Cite

BackgroundImmune checkpoint inhibitors (ICIs) therapy can be complicated by their potential cardiovascular toxicities, including myocarditis. Nowadays, no prospective trials have focused on ICI-associated myocarditis optimized management. Available evidence only come from case reports or series. A systematic case reports analysis was conducted to collect and evaluate emerging evidence of ICI-associated myocarditis to provide more information to clinicians.MethodsWe performed a literature search for eligible case reports or series published between January 2018 and May 2023 using the PubMed database. Then, we extracted interesting information via table form. Finally, this study included 113 publications on 106 patients with ICI-associated myocarditis.ResultsMyocarditis was found to be a highly life-threatening disease, with 53.8% of cases. Over half of cases were life-threatening (G4, 23.6%) or severe (G3, 35.8%) and required glucocorticoids. Higher rates of improvement were associated with the best response to ICI for complete response/partial response (72.7% vs. 53.9%), glucocorticoid administration (30% vs. 22%), and discontinuation of ICI (58.8% vs. 32.1%). Consequently, ICI-associated G3–G4 myocarditis should be treated with a combination of discontinuation of ICIs, high-dose glucocorticoids, other drugs, chemical drugs, plasma exchange, and life support. For moderate G1 or G2 cases, discontinuation of ICIs and regular-dose glucocorticoids should be considered.ConclusionOnce full recovery or improvement was achieved; glucocorticoids can be administered at low doses or stopped. Notably, re-challenge with ICIs appears feasible after resolution or meaningful improvement of myocarditis.

show abstract

Section: Discussionmentioning

confidence: 99%

Immune checkpoint inhibitor–associated myocarditis: a systematic analysis of case reports

Wang,

Zhao,

Zhang

et al. 2023

Front. Immunol.

View full text Add to dashboard Cite

show abstract

“…At the same time, our results suggested that the use of PD-1, PD-L1 or CTLA4 inhibitors in the treatment of patients with advanced TETs required close attention on the generation of immune-related adverse reactions such as MG while treating tumors. Anti-PD-L1 or anti-PD-1 antibodies have been reported to cause adverse reactions such as MG, myocarditis and pneumonia in patients with TETs [ 32 – 35 ]. Further, our study provides multiple potential immunotherapeutic targets such as CD2.…”

Section: Discussionmentioning

confidence: 99%

Thymic epithelial tumors: examining the GTF2I mutation and developing a novel prognostic signature with LncRNA pairs to predict tumor recurrence

et al. 2022

View full text Add to dashboard Cite

Background General transcription factor IIi (GTF2I) mutations are very common in thymic epithelial tumors (TETs) and are related to a more favorable prognosis in TET patients. However, limited research has been conducted on the role of GTF2I in the tumor immune microenvironment (TIME). Further, long non-coding RNAs (lncRNAs) have been associated with the survival of patients with TETs. Therefore, this study aimed to explore the relationship between GTF2I mutations and TIME and build a new potential signature for predicting tumor recurrence in the TETs. Research data was downloaded from The Cancer Genome Atlas database and the CIBERSORT algorithm was used to evaluate TIME differences between GTF2I mutant and wild-type TETs. Relevant differentially expressed lncRNAs based on differentially expressed immune-related genes were identified to establish lncRNA pairs. We constructed a signature using univariate and multivariate Cox regression analyses. Results GTF2I is the most commonly mutated gene in TETs, and is associated with an increased number of early-stage pathological types, as well as no history of myasthenia gravis or radiotherapy treatment. In the GTF2I wild-type group, immune score and immune cell infiltrations with M2 macrophages, activated mast cells, neutrophils, plasma, T helper follicular cells, and activated memory CD4 T cells were higher than the GTF2I mutant group. A risk model was built using five lncRNA pairs, and the 1-, 3-, and 5-year area under the curves were 0.782, 0.873, and 0.895, respectively. A higher risk score was related to more advanced histologic type. Conclusion We can define the GTF2I mutant-type TET as an immune stable type and the GTF2I wild-type as an immune stressed type. A signature based on lncRNA pairs was also constructed to effectively predict tumor recurrence.

show abstract

“…These immune-related adverse events most commonly involve hepatitis, colitis, myocarditis and dysregulations of endocrine systems including the pancreas and adrenal glands ( 52 ). Interestingly, several reports showed that ATG is able to counteract adverse events caused by immune checkpoint inhibition ( 53-55 ). While this effect is in part explainable by its T-cell depleting properties, based on our data, it is tempting to speculate that induction of PDL-1 on monocytes, or other cell types, potentially contributes to the inhibition of autoreactive T-cells, resulting in an amelioration of the reported adverse effects.…”

Section: Discussionmentioning

confidence: 99%

Antithymocyte globulin inhibits CD8⁺ T cell effector functions via the paracrine induction of PDL-1 on monocytes

Copic

Direder

Klas

et al. 2022

Preprint

View full text Add to dashboard Cite

Antithymocyte globulins (ATG) are T cell depleting antibodies used in solid organ transplantation for induction therapy in sensitized patients with high risk of graft rejection. Previously described effects besides depletion of T cells suggest additional modes of action and identified further cellular targets. Here, we examined the transcriptional changes arising in immune cells from human blood after ex vivo stimulation with ATG on a single cell level to uncover additional mechanisms by which ATG regulates T cell activity and effector functions. Analysis of the paracrine factors present in plasma of ATG-treated whole blood revealed high levels of chemokines and cytokines including Interferon-γ (IFN-γ). Furthermore, we identify an increase of surface expression of programmed death ligand 1 (PDL-1) on monocytes mediated by the released paracrine factors. In addition, we show that this induction is dependent on activation of JAK/STAT signaling via binding of IFN-γ to Interferon-γ receptor 1 (IFN-γR1). Lastly, we demonstrate that the modulation of the immune-regulatory axis of Programmed cell death protein 1 (PD-1) on activated CD8+ T cells with PDL-1 found on monocytes mediated by ATG potently inhibits effector functions including proliferation and granzyme B release of activated T cells. Together our findings represent a novel mode of action by which ATG exerts its immunosuppressive effects.

show abstract

Checkpoint inhibitor-induced fulminant myocarditis, complete atrioventricular block and myasthenia gravis—a case report

Cited by 18 publications

References 11 publications

Immune checkpoint inhibitor–associated myocarditis: a systematic analysis of case reports

Immune checkpoint inhibitor–associated myocarditis: a systematic analysis of case reports

Thymic epithelial tumors: examining the GTF2I mutation and developing a novel prognostic signature with LncRNA pairs to predict tumor recurrence

Antithymocyte globulin inhibits CD8⁺ T cell effector functions via the paracrine induction of PDL-1 on monocytes

Contact Info

Product

Resources

About

Checkpoint inhibitor-induced fulminant myocarditis, complete atrioventricular block and myasthenia gravis—a case report

Cited by 18 publications

References 11 publications

Immune checkpoint inhibitor–associated myocarditis: a systematic analysis of case reports

Immune checkpoint inhibitor–associated myocarditis: a systematic analysis of case reports

Thymic epithelial tumors: examining the GTF2I mutation and developing a novel prognostic signature with LncRNA pairs to predict tumor recurrence

Antithymocyte globulin inhibits CD8+ T cell effector functions via the paracrine induction of PDL-1 on monocytes

Contact Info

Product

Resources

About

Antithymocyte globulin inhibits CD8⁺ T cell effector functions via the paracrine induction of PDL-1 on monocytes