Immune checkpoint blockade in HIV.

Immune checkpoint blockade in HIV.
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艾滋病病毒的免疫检查点封锁。

DOI:
10.1016/j.ebiom.2022.103840
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发表时间:
2022-03
期刊:
影响因子:
11.1
通讯作者:
Rasmussen TA
Rasmussen TA
中科院分区:
医学1区
文献类型:
--
作者:
Gubser C;Chiu C;Lewin SR;Rasmussen TA

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抗逆转录病毒疗法(ART)大大提高了艾滋病毒感染者(PWH)的预期寿命,并有助于恢复免疫功能,但不能治愈,必须终身服用。在没有ART的情况下实现对HIV的长期控制可能需要强大的T细胞功能,但慢性HIV感染与即使在ART上也持续存在的免疫衰竭有关。这是由向T细胞提供负信号的免疫检查点的表达升高驱动的。在患有癌症的个体中,免疫检查点阻断增强了肿瘤导向的T细胞应答,从而导致显著的临床治愈。因此,如果ICB可以通过逆转HIV潜伏期和/或驱动HIV特异性T细胞的恢复来有助于HIV治愈或缓解,则存在高度兴趣。我们在此回顾了免疫检查点在持续性HIV感染中的作用的最新证据,并讨论了采用免疫检查点阻断作为靶向抗逆转录病毒治疗中HIV持续性的治疗方法的潜力。
Antiretroviral therapy (ART) has dramatically improved life expectancy for people with HIV (PWH) and helps to restore immune function but is not curative and must be taken lifelong. Achieving long term control of HIV in the absence of ART will likely require potent T cell function, but chronic HIV infection is associated with immune exhaustion that persists even on ART. This is driven by elevated expression of immune checkpoints that provide negative signalling to T cells. In individuals with cancer, immune checkpoint blockade augments tumour-directed T-cell responses resulting in significant clinical cures. There is therefore high interest if ICB can contribute to HIV cure or remission by reversing HIV-latency and/or drive recovery of HIV-specific T-cells. We here review recent evidence on the role of immune checkpoints in persistent HIV infection and discuss the potential for employing immune checkpoint blockade as a therapeutic approach to target HIV persistence on ART.
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