Despite successful combined antiretroviral therapy (cART), the risk of non-AIDS defining cancers (NADCs) remains higher for HIV-infected individuals than the general population. The reason for this increase is highly disputed. Here, we hypothesized that T-cell receptor (TCR) γδ cells and/or mucosal-associated invariant T (MAIT) cells might be associated with the increased risk of NADCs. γδ T cells and MAIT cells both serve as a link between the adaptive and the innate immune system, and also to exert direct anti-viral and anti-tumor activity. We performed a longitudinal phenotypic characterization of TCR γδ cells and MAIT cells in HIV-infected individuals developing Hodgkin’s lymphoma (HL), the most common type of NADCs. Cryopreserved PBMCs of HIV-infected individuals developing HL, matched HIV-infected controls without (w/o) HL and healthy controls were used for immunophenotyping by polychromatic flow cytometry, including markers for activation, exhaustion and chemokine receptors. We identified significant differences in the CD4+ T cell count between HIV-infected individuals developing HL and HIV-infected matched controls within 1 year before cancer diagnosis. We observed substantial differences in the cellular phenotype mainly between healthy controls and HIV infection irrespective of HL. A number of markers tended to be different in Vδ1 and MAIT cells in HIV+HL+ patients vs. HIV+ w/o HL patients; notably, we observed significant differences for the expression of CCR5, CCR6 and CD16 between these two groups of HIV+ patients. TCR Vδ1 and MAIT cells in HIV-infected individuals developing HL show subtle phenotypical differences as compared to the ones in HIV-infected controls, which may go along with functional impairment and thereby may be less efficient in detecting and eliminating malignant cells. Further, our results support the potential of longitudinal CD4+ T cell count analysis for the identification of patients at higher risk to develop HL.

中文翻译：

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感染霍奇金淋巴瘤的HIV感染者中TCRγδT细胞和MAIT细胞的免疫表型特征

尽管成功地采用了联合抗逆转录病毒疗法（cART），但受HIV感染的个体非艾滋病定义的癌症（NADC）的风险仍然高于普通人群。这种增加的原因是高度有争议的。在这里，我们假设T细胞受体（TCR）γδ细胞和/或与粘膜相关的不变T（MAIT）细胞可能与NADCs风险增加有关。γδT细胞和MAIT细胞既充当适应性免疫系统与先天免疫系统之间的纽带，也发挥直接的抗病毒和抗肿瘤活性。我们在发展霍奇金淋巴瘤（HL）（最常见的NADC类型）的HIV感染者中进行了TCRγδ细胞和MAIT细胞的纵向表型表征。患有HL的HIV感染者的冷冻保存的PBMC，将匹配的无（无）HL的HIV感染对照和健康对照用于多色流式细胞术的免疫表型分析，包括激活，衰竭和趋化因子受体的标志物。我们在癌症诊断前1年内，发现发展为HL的HIV感染者与HIV感染的配对对照之间的CD4 + T细胞计数存在显着差异。我们观察到主要在健康对照和HIV感染之间的细胞表型上存在实质性差异，而与HL无关。HIV + HL +患者与HIV + w / o HL患者的Vδ1和MAIT细胞中的许多标志物往往有所不同。值得注意的是，我们观察到这两组HIV +患者之间CCR5，CCR6和CD16的表达存在显着差异。与感染HIV的对照组相比，发展为HL的HIV感染者中TCRVδ1和MAIT细胞表现出细微的表型差异，这可能伴随功能受损，因此检测和消除恶性细胞的效率可能较低。此外，我们的结果支持纵向CD4 + T细胞计数分析在识别罹患HL的较高风险患者中的潜力。