The impact of immune checkpoint therapy on the latent reservoir in HIV-infected individuals with cancer on antiretroviral therapy.
The impact of immune checkpoint therapy on the latent reservoir in HIV-infected individuals with cancer on antiretroviral therapy.
复制标题
DOI：
10.1097/qad.0000000000002919
复制
发表时间：
2021-08-01
期刊：
影响因子：
--
通讯作者：
Rasmussen TA
中科院分区：
文献类型：
--
作者：
Lau JSY;McMahon JH;Gubser C;Solomon A;Chiu CYH;Dantanarayana A;Chea S;Tennakoon S;Zerbato JM;Garlick J;Morcilla V;Palmer S;Lewin SR;Rasmussen TA
量化接受免疫检查点阻断（ICB）的恶性肿瘤患者接受抗逆转录病毒治疗（ART）的HIV感染者（PLWH）的HIV特异性免疫学和病毒学变化。在接受ART的HIV阳性成人中，在ICB的四个周期之前和之后收集血液样本。对CD 4 + T细胞进行的病毒学评估包括：细胞相关（CA）未剪接（US）HIV RNA、细胞相关（CA）HIV DNA、达特/rev诱导有限稀释测定（TILDA）和使用单拷贝测定（SCA）的血浆HIV RNA。采用流式细胞术评估前体耗竭T细胞（Tpex）和耗竭T细胞（Tex）的频率，以及通过细胞内细胞因子染色（ICS）对IFN-γ、TNF-α或CD 107 a呈阳性的GAG特异性CD 4+和CD 8 + T细胞的频率。参与者（P）1接受avelumab（抗PD-L1）治疗默克尔细胞癌。P2和P3接受ipilimumab（抗CTLA-4）和nivolumab（抗PD-1）治疗转移性黑色素瘤。在所有3名参与者中观察到每次输注后CA-US RNA增加。HIV DNA或具有可诱导MS HIV RNA的细胞比例没有一致的变化。P2显示，在抗PD 1和抗CTLA-4后，产生IFN-γ、TNF-α和CD 107 a的gag特异性中枢和效应记忆CD 8 + T细胞的频率显著增加。ICB前CD 8 + Tpex细胞的频率在该参与者中也最高。在三个PLWH癌症ART，我们发现，ICB激活潜伏的HIV和增强HIV特异性T细胞功能，但有相当大的变化。
To quantify HIV specific immunological and virological changes in people living with HIV (PLWH) on antiretroviral therapy (ART) with malignancy who received immune checkpoint blockade (ICB). Observational cohort study Blood samples were collected before and after four cycles of ICB in HIV positive adults on ART. Virological assessments performed on CD4+ T cells included: cell associated (CA) unspliced (US) HIV RNA, cell associated (CA) HIV DNA, Tat/rev Induced Limiting Dilution Assay (TILDA), and plasma HIV RNA using a single copy assay (SCA). Flow cytometry was used to assess the frequency of precursor exhausted T cells (Tpex) and exhausted T cells (Tex), and Gag-specific CD4+ and CD8+ T cells positive for IFN-γ, TNF-α, or CD107a by intracellular cytokine staining (ICS). Participant (P)1 received avelumab (anti-PD-L1) for Merkel cell carcinoma. P2 and P3 received ipilimumab (anti-CTLA-4) and nivolumab (anti-PD-1) for metastatic melanoma. An increase in CA-US RNA following each infusion was noted in all 3 participants. There were no consistent changes in HIV DNA or the proportion of cells with inducible MS HIV RNA. P2 demonstrated a striking increase in the frequency of gag-specific central and effector memory CD8+ T cells producing IFN-γ, TNF-α, and CD107a following anti-PD1 and anti-CTLA-4. The frequency of CD8+ Tpex cells pre-ICB was also highest in this participant. In three PLWH with cancer on ART, we found that ICB activated latent HIV and enhanced HIV-specific T cell function but with considerable variation.