PD-1 inhibitors-associated myocarditis in non-small cell lung cancer patients

Figures

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  Figure 1. Clinical presentation of patients with ICI-associated myocarditis. (A) Time from ICI to myocarditis onset to follow-up deadline in each of the 14 cases. ICI was administered on day 0. And the follow-up deadline is December 31, 2020, except for lost follow-up or death. After the cardiotoxicity onset, 8 patients received rescue in critical condition. Finally, 10 patients were discharged after improvement, while patients #2, 3, 4, 7 were discharged themselves against the advice of doctors. (B) A description of the results for the ECG. (C) A description of the results for troponin. ICI, immune checkpoint inhibitor; ECG, electrocardiogram.

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  Figure 2. Laboratory examination of cardiac biomarkers and related biochemical indexes. Since the different normal value ranges of each indicator, all actual values are converted to the fold change of normal values for comparing different indicators. (A) Admission, peak and discharge levels of five myocardial injury biomarkers of 13 cases. *, P<0.05; **, P<0.01. (B,C) Two heat maps show the peak levels of laboratory biomarkers in various patients during hospitalization. (B) This heat map shows eight key biomarkers. Due to a few Maxima, fold change values are converted to log10 (fold change), therefore, 0 means the normal value. (C) This heat map shows inflammatory cells and cytokines, etc. White rectangle means the missing value. cTnI, cardiac troponin I; CK-MB, creatine kinase-MB; CK, creatine kinase; LDH, lactic dehydrogenase; Mb, myoglobin; pro-BNP, pro-B-type natriuretic peptide; D-d, D-dimer; IL, interleukin; WBC, white blood cell; NK cell, natural killer cell; MONO, monocyte; IgG, immunoglobin G; TNF, tumor necrosis factor; IFN, interferon.

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  Figure 3. HE and IHC staining of endomyocardial biopsy. This myocardial tissue was obtained from patient #9, 23 days after the onset of myocarditis, which was in a stable condition. A small number of fibers around the muscle bundle became smaller, and a small number of lymphocytes infiltrated around individual small vessels (30 lymphocytes/foci). (A-C) HE staining shows increased fatty tissue, tissue fibrosis and lymphocytic infiltration. All scale bars in this figure denote 50 µm. (D) Medium quantity of CD3-positive T lymphocytes, CD3 IHC staining. (E) Rare CD4-positive T lymphocyte infiltrate, CD4 IHC staining. (F) A small number of CD8-positive T lymphocytes, CD8 IHC staining. (G) Limited CD20-positive B lymphocyte infiltrate, CD20 IHC staining. (H) Moderate CD68-positive macrophage infiltrate, CD68 IHC staining. HE, hematoxylin-eosin; IHC, immunohistochemical.