Fungal Pathogenesis Section, Laboratory of Clinical Immunology and Microbiology (LCIM), National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD, USA.
Fungal Pathogenesis Section, Laboratory of Clinical Immunology and Microbiology (LCIM), National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD, USA.
Trends Mol Med. 2019 Dec;25(12):1080-1093. doi: 10.1016/j.molmed.2019.08.004. Epub 2019 Sep 4.
The mammalian immune system has evolved the capacity to detect and destroy tumor cells. Tumors utilize multiple strategies to evade host immune surveillance, including the induction of the checkpoint molecules cytotoxic T lymphocyte-associated protein 4 (CTLA-4) and programmed cell death protein 1 (PD-1) to suppress antitumor immunity. Pharmacologic blockade of these molecules with checkpoint inhibitors (CPIs) restores T cell function and prolongs survival in patients with various malignancies. Emerging evidence suggests that the same checkpoint pathways may play a crucial role during infections. Indeed, CPIs appear promising as immunotherapeutic agents in infectious diseases, although their efficacy varies depending on pathogen-, cell-, and organ-specific factors. More research will be necessary to clarify the effects and safety of CPIs on clinically relevant outcomes of human infection.
哺乳动物的免疫系统已经进化出了检测和摧毁肿瘤细胞的能力。肿瘤利用多种策略来逃避宿主的免疫监视，包括诱导检查点分子细胞毒性 T 淋巴细胞相关蛋白 4（CTLA-4）和程序性细胞死亡蛋白 1（PD-1）来抑制抗肿瘤免疫。用检查点抑制剂（CPIs）阻断这些分子可以恢复 T 细胞的功能，并延长各种恶性肿瘤患者的生存期。新出现的证据表明，相同的检查点途径可能在感染过程中发挥关键作用。事实上，CPIs 作为传染病的免疫治疗药物有很大的应用前景，尽管它们的疗效因病原体、细胞和器官特异性因素而异。需要进一步的研究来阐明 CPIs 对人类感染的临床相关结局的影响和安全性。
