Belizário José, Destro Rodrigues Maria Fernanda
Department of Pharmacology, Institute Biomedical Sciences of the University of Sao Paulo, Avenida Lineu Prestes, 1524, São Paulo, CEP 05508-900, Brazil.
Postgraduate Program in Biophotonics Applied to Health Science, Nove de Julho University, São Paulo, SP, Brazil.
Ther Adv Vaccines Immunother. 2020 Mar 13;8:2515135520904238. doi: 10.1177/2515135520904238. eCollection 2020.
CD8 T-cell exhaustion is a dysfunctional state that is regulated through the expression of inhibitory checkpoint receptor genes including the cytotoxic T-lymphocyte-associated antigen 4, programmed death 1, and DNA methylation of effector genes interferon-γ, perforin, and granzyme B. Different strategies have been used to reverse T-cell exhaustion, which is an adverse event of checkpoint inhibitor blockade. Here, we present the mechanisms by which DNA methyltransferase inhibitors and Simian virus 40 large T antigen through viral mimicry can promote the reversion of exhausted CD8 T cells. We examine how these pharmacological strategies can work together to improve the clinical efficacy of immunotherapies.
CD8 T细胞耗竭是一种功能失调状态，通过抑制性检查点受体基因的表达来调节，这些基因包括细胞毒性T淋巴细胞相关抗原4、程序性死亡蛋白1，以及效应基因干扰素-γ、穿孔素和颗粒酶B的DNA甲基化。已经采用了不同策略来逆转T细胞耗竭，这是检查点抑制剂阻断的一种不良事件。在此，我们阐述了DNA甲基转移酶抑制剂和猿猴病毒40大T抗原通过病毒模拟促进耗竭的CD8 T细胞逆转的机制。我们研究了这些药理学策略如何协同作用以提高免疫疗法的临床疗效。
