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Immunomodulatory treatment of immune checkpoint inhibitor-induced myocarditis: Pathway toward precision-based therapy.

免疫检查点抑制剂诱导的心肌炎的免疫调节治疗: 走向精准治疗的途径。

  • 影响因子:1.96
  • DOI:10.1016/j.carpath.2020.107211
  • 作者列表:"Balanescu DV","Donisan T","Palaskas N","Lopez-Mattei J","Kim PY","Buja LM","McNamara DM","Kobashigawa JA","Durand JB","Iliescu CA
  • 发表时间:2020-01-01
Abstract

:Immune checkpoint inhibitor (ICI)-induced myocarditis carries a poor prognosis and is not fully understood. Similar to lymphocytic myocarditis and acute cellular rejection in heart transplant, ICI-induced myocarditis requires immune suppressive strategies. We aimed to describe ICI-induced myocarditis by presenting findings of comprehensive cardiovascular evaluations and outcomes of patients following a therapeutic approach similar to autoimmune disorders or allograft transplant rejection, and to discuss the molecular basis of the benefits of immune modulation and statins in ICI-myocarditis. Three patients with ICI-induced myocarditis (2 with positive biopsies and 1 based on cardiac magnetic resonance imaging with negative biopsy) underwent a complete cardiovascular workup, including cardiac catheterization with endomyocardial biopsy. Treatment was with intravenous immunoglobulins (IVIG) and statins in all cases, with additional colchicine (2 cases) or hydroxychloroquine (1 case). Immunohistochemical analysis demonstrated varied subsets of T cells involved in the inflammatory response. Therapy with IVIG and statins led to symptom resolution and cardiac function normalization at 1-month follow-up in all patients. Cancer therapy was resumed in all patients. One patient expired 10 months after the myocarditis episode due to advanced malignancy; two patients were alive, free of heart failure symptoms and cancer progression, at 1-year follow-up, and 1 patient was rechallenged with ICI. We suggest that treatment with IVIG and statins may allow for a prompt resumption of anti-cancer therapy (including ICI) and improve outcomes.

摘要

: 免疫检查点抑制剂 (ICI) 诱导的心肌炎预后不良,尚不完全清楚。与心脏移植中的淋巴细胞性心肌炎和急性细胞性排斥反应相似,ICI诱导的心肌炎需要免疫抑制策略。我们旨在通过展示综合心血管评价的结果和患者接受类似于自身免疫性疾病或同种异体移植排斥反应的治疗方法的结果来描述ICI诱导的心肌炎。并探讨免疫调节和他汀类药物在ICI-心肌炎中获益的分子基础。3 例ICI引起的心肌炎患者 (2 例活检阳性,1 例基于心脏磁共振成像活检阴性) 接受了完整的心血管检查,包括心内膜心肌活检的心导管检查。所有病例均采用静脉注射免疫球蛋白 (IVIG) 和他汀类药物治疗,加用秋水仙碱 (2 例) 或羟氯喹 (1 例)。免疫组织化学分析显示参与炎症反应的T细胞的不同亚群。IVIG和他汀类药物治疗导致所有患者在 1 个月随访时症状缓解和心功能正常化。所有患者均恢复癌症治疗。1 例患者在晚期恶性肿瘤心肌炎发作 10 个月后到期; 2 例患者存活,1 年随访时无心力衰竭症状和癌症进展,1 例患者再次接受ICI治疗。我们建议用IVIG和他汀类药物治疗可能允许立即恢复抗癌治疗 (包括ICI) 并改善结局。

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影响因子:0.96
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皮肤肿瘤方向

皮肤肿瘤是发生在皮肤的细胞增生性疾病,是一种常见病。发生于皮内或皮下组织的新生物,种类很多,临床上分良性肿瘤和恶性肿瘤。恶性肿瘤可以不断增殖,引起转移,威胁生命,称为皮肤癌。

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