Leal Fabio E, Premeaux Thomas A, Abdel-Mohsen Mohamed, Ndhlovu Lishomwa C
Programa de Oncovirologia, Instituto Nacional de Cancer , Rio de Janeiro , Brazil.
Department of Tropical Medicine, Hawaii Center for AIDS, John A. Burns School of Medicine, University of Hawaii , Honolulu, HI , USA.
Front Immunol. 2017 Mar 21;8:315. doi: 10.3389/fimmu.2017.00315. eCollection 2017.
Now in its fourth decade, the burden of HIV disease still persists, despite significant milestone achievements in HIV prevention, diagnosis, treatment, care, and support. Even with long-term use of currently available antiretroviral therapies (ARTs), eradication of HIV remains elusive and now poses a unique set of challenges for the HIV-infected individual. The occurrence of HIV-associated non-AIDS-related comorbidities outside the scope of AIDS-defining illnesses, in particular non-AIDS-defining cancers, is much greater than the age-matched uninfected population. The underlying mechanism is now recognized in part to be related to the immune dysregulated and inflammatory status characteristic of HIV infection that persists despite ART. Natural killer (NK) cells are multifunctional effector immune cells that play a critical role in shaping the innate immune responses to viral infections and cancer. NK cells can modulate the adaptive immune response their role in dendritic cell (DC) maturation, removal of immature tolerogenic DCs, and their ability to produce immunoregulatory cytokines. NK cells are therefore poised as attractive therapeutic targets that can be harnessed to control or clear both HIV and HIV-associated malignancies. To date, features of the tumor microenvironment and the evolution of NK-cell function among individuals with HIV-related malignancies remain unclear and may be distinct from malignancies observed in uninfected persons. This review intends to uncouple anti-HIV and antitumor NK-cell features that can be manipulated to halt the evolution of HIV disease and HIV-associated malignancies and serve as potential preventative and curative immunotherapeutic options.
如今，尽管在艾滋病病毒（HIV）的预防、诊断、治疗、护理及支持方面取得了重大里程碑式的成就，但HIV疾病的负担依然存在。即便长期使用现有的抗逆转录病毒疗法（ART），HIV的根除仍难以实现，并且目前给HIV感染者带来了一系列独特的挑战。在定义艾滋病的疾病范围之外，与HIV相关的非艾滋病相关合并症的发生，尤其是非艾滋病定义的癌症，比年龄匹配的未感染人群要多得多。现在部分认识到其潜在机制与HIV感染的免疫失调和炎症状态有关，尽管接受了ART治疗，这种状态依然持续。自然杀伤（NK）细胞是多功能效应免疫细胞，在塑造针对病毒感染和癌症的固有免疫反应中发挥关键作用。NK细胞可以调节适应性免疫反应——它们在树突状细胞（DC）成熟、清除未成熟的耐受性DC以及产生免疫调节细胞因子的能力方面发挥作用。因此，NK细胞有望成为有吸引力的治疗靶点，可用于控制或清除HIV以及与HIV相关的恶性肿瘤。迄今为止，HIV相关恶性肿瘤患者的肿瘤微环境特征和NK细胞功能的演变仍不清楚，可能与未感染人群中观察到的恶性肿瘤不同。本综述旨在剖析可被操控以阻止HIV疾病和HIV相关恶性肿瘤演变的抗HIV和抗肿瘤NK细胞特征，并作为潜在的预防性和治愈性免疫治疗选择。
