Cardiotoxicity caused by chemotherapeutics such as anthracyclines is well recognized. In recent years, immunotherapy has been successfully introduced in cancer treatment. Unfortunately, cardiotoxicity seems to have emerged as an issue in recent reports.¹

For decades, immunologists and oncologists have attempted to stimulate antitumor immune responses to fight cancer. Initial attempts displayed marginal success because several inhibitory pathways such as cytotoxic T lymphocyte–associated protein 4 (CTLA-4), programmed cell death protein 1 (PD-1), and programmed cell death ligand 1 (PD-L1) dampen the antitumor functions of T lymphocytes. Tumors exploit these pathways to escape T cell–mediated tumor-specific immunity. Monoclonal antibodies targeting CTLA-4 (ipilimumab), PD-1 (nivolumab and pembrolizumab), and PD-L1 (atezolizumab, avelumab, durvalumab), called immune checkpoint inhibitors (ICIs), have revolutionized cancer treatments. However, dramatic responses are currently confined to few patients, presumably because of the complex network of immunosuppressive pathways in tumor microenvironments. Combined anti–CTLA-4 and anti–PD-1 blockade further enhances antitumor activity (Figure, A). ICIs are being tested in HIV-infected patients, characterized by overexpression of immune checkpoints and T-cell exhaustion.

Mechanism of action of checkpoint inhibitors. A, Tumor cells escape immune surveillance by promoting checkpoint activation.Tumor cells express the immune checkpoint activator programmed cell death ligand 1 (PD-L1) and produce antigens (blue dots) that are captured by antigen-presenting cells (APCs). These cells present antigens to cytotoxic CD8⁺ T cells through the interaction of major histocompatibility complex (MHC) molecules and T-cell receptor (TCR). T-cell activation requires costimulatory signals mediated by the interaction between B7 and CD28. Inhibitory …

由化疗药（如蒽环类药物）引起的心脏毒性已广为人知。近年来，免疫疗法已成功地引入癌症治疗中。不幸的是，在最近的报道中似乎已经出现了心脏毒性问题。^1个

数十年来，免疫学家和肿瘤学家一直试图刺激抗肿瘤免疫反应来对抗癌症。最初的尝试显示出一定的成功，因为细胞抑制性T淋巴细胞相关蛋白4（CTLA-4），程序性细胞死亡蛋白1（PD-1）和程序性细胞死亡配体1（PD-L1）等几种抑制途径会抑制抗肿瘤功能。 T淋巴细胞。肿瘤利用这些途径逃避了T细胞介导的肿瘤特异性免疫。靶向CTLA-4（ipilimumab），PD-1（nivolumab和pembrolizumab）和PD-L1（atezolizumab，avelumab，durvalumab）的单克隆抗体被称为免疫检查点抑制剂（ICIs），彻底改变了癌症治疗方法。但是，目前的戏剧性反应仅限于少数患者，这可能是由于肿瘤微环境中免疫抑制途径的复杂网络所致。抗-CTLA-4和抗-PD-1联用可进一步增强抗肿瘤活性（图A）。ICI正在HIV感染的患者中进行测试，其特征在于免疫检查点的过度表达和T细胞衰竭。

检查点抑制剂的作用机理。A，肿瘤细胞通过促进检查点激活逃避了免疫监视。肿瘤细胞表达免疫检查点激活剂编程的细胞死亡配体1（PD-L1），并产生被抗原呈递细胞（APC）捕获的抗原（蓝点）。这些细胞通过主要组织相容性复合体（MHC）分子与T细胞受体（TCR）的相互作用将抗原呈递给细胞毒性CD8 ⁺ T细胞。T细胞激活需要B7和CD28之间相互作用介导的共刺激信号。抑制性...