Myocarditis Induced by Immune Checkpoint Inhibitors: Mechanisms and Therapeutic Prospects

Figures & data

Figure 1 Mechanism of PD-1 and CTLA-4 in inhibiting T cell activation.

Abbreviations: TIM-3, T cell immunoglobulin domain and mucin domain-3; LAG-3, Lymphocyte activation gene-3; TCR, T cell receptor; TIGIT, T cell immunoreceptor with Ig and ITIM domains; AKT, protein kinase; Bcl-xl, B cell lymphoma xl; ZAP70, zeta-chain-associated protein kinase 70.

Table 1 FDA-Approved 7 Kinds of Immune Checkpoint Inhibitors

Target Pathway	Agent	IgG Class	Company	Approved Cancer	References
CTLA-4	Ipilimumab	Human IgG1	Bristol-Meyers Squibb	Melanoma	[^Citation37]
	Tremelimumab	Human IgG2	AstraZeneca	Malignant mesothelioma	[^Citation38]
PD-1	Pembrolizumab	Humanized IgG4	Merck	Melanoma	[^Citation39]
				Lung cancer	[^Citation40,^Citation41]
				Head and neck cancer	[^Citation42]
	Nivolumab	Human IgG4	Bristol-Meyers Squibb/Ono	Melanoma	[^Citation11]
			Colorectal cancer	Non-small cell lung cancer	[^Citation43,^Citation44]
				Kidney cancer	[^Citation45]
				Hodgkin’s lymphoma	[^Citation46]
				Squamous cell carcinoma of the head and neck	[^Citation47]
				Urothelial carcinoma	[^Citation48]
				Hepatocellular carcinoma	[^Citation49]
PD-L1	Atezolizumab	Humanized IgG1k	Roche/Genentech	Urothelial cancer	[^Citation50]
				Non-small cell lung cancer	[^Citation51]
	Durvalumab	Human IgG1k	Medimmune/AstraZeneca	Urothelial cancer	[^Citation53]
				Non-small cell lung cancer	[^Citation54]
				Small cell lung cancer	[^Citation55]
	Avelumab	Human IgG1	Merck Serono/Pfizer	Meckel cell carcinoma	[^Citation56]
				Urothelial cancer	[^Citation57]

Figure 2 Anti-PD-1 therapy breaks the peripheral immune tolerance by unleashing effective T cells.

Abbreviations: DC, dendritic cell; CXCL10, CXCchemokineligand-10; TNF- α, tumor necrosis factor alpha.

Figure 3 Proposed algorithm for work-up and management of ICI-mediated myocarditis.

Abbreviations: ECG, electrocardiogram; cTns, cardiac troponins; CK-MB, creatine kinase isoenzyme-MB; CMR, cardiac magnetic resonance imaging; NT-proBNP, N-terminal-pro-brain natriuretic peptide.

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