PDF(Pubmed)
Abstract：
Relapse is the most frequent cause of treatment failure after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Natural killer (NK) cells and γδ T cells reconstitute early after allo-HSCT, contribute to tumor immunosurveillance via major histocompatibility complex-independent mechanisms and do not induce graft-versus-host disease. Here we performed a quantitative and qualitative analysis of the NK and γδ T cell repertoire in healthy individuals, recipients of HLA-matched sibling or unrelated donor allo-HSCT (MSD/MUD-HSCT) and umbilical cord blood-HSCT (UCB-HSCT). NK cells are present at high frequencies in all allo-HSCT recipients. Immune reconstitution (IR) of vδ2+ cells depended on stem cell source. In MSD/MUD-HSCT recipients, vδ2+ comprise up to 8% of the total lymphocyte pool, whereas vδ2+ T cells are barely detectable in UCB-HSCT recipients. Vδ1+ IR was driven by CMV reactivation and was comparable between MSD/MUD-HSCT and UCB-HSCT. Strategies to augment NK cell mediated tumor responses, similar to IL-15 and antibodies, also induced vδ2+ T cell responses against a variety of different tumor targets. Vδ1+ γδ T cells were induced less by these same stimuli. We also identified elevated expression of the checkpoint inhibitory molecule TIGIT (T cell Ig and ITIM domain), which is also observed on tumor-infiltrating lymphocytes and epidermal γδ T cells. Collectively, these data show multiple strategies that can result in a synergized NK and γδ T cell antitumor response. In the light of recent developments of low-toxicity allo-HSCT platforms, these interventions may contribute to the prevention of early relapse.
摘要：
复发是异基因造血干细胞移植（allo-HSCT）后治疗失败的最常见原因。自然杀伤（NK）细胞和γδT细胞在allo-HSCT后早期重建，通过主要的组织相容性复合物非依赖性机制有助于肿瘤免疫监视，并且不诱导移植物抗宿主病。在这里，我们对健康个体的NK和γδT细胞库进行了定量和定性分析，HLA匹配的同胞或无关供体allo-HSCT（MSD/MUD-HSCT）和脐带血-HSCT（UCB-HSCT）的接受者。NK细胞以高频率存在于所有同种异体HSCT接受者中。vδ2细胞的免疫重建（IR）取决于干细胞来源。在MSD/MUD-HSCT收件人中，vδ2+占总淋巴细胞池的8％，而vδ2+T细胞在UCB-HSCT受体中几乎检测不到。Vδ1IR由CMV再激活驱动，在MSD/MUD-HSCT和UCB-HSCT之间具有可比性。增强NK细胞介导的肿瘤反应的策略，类似于IL-15和抗体，还诱导了针对多种不同肿瘤靶标的vδ2+T细胞应答。Vδ1γδT细胞受这些相同刺激的诱导较少。我们还确定了检查点抑制分子TIGIT（T细胞Ig和ITIM结构域）的表达升高，在肿瘤浸润淋巴细胞和表皮γδT细胞上也观察到。总的来说，这些数据显示多种策略可导致协同的NK和γδT细胞抗肿瘤应答。鉴于低毒性allo-HSCT平台的最新发展，这些干预措施可能有助于预防早期复发.
