不适合移植的大 B 细胞淋巴瘤二线使用 axicabtagene ciloleucel:ALYCANTE 最终分析
Second-line axicabtagene ciloleucel in large B-cell lymphoma ineligible for transplantation: ALYCANTE final analysis.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Phenotypic and functional analysis of γδ T cells in the pathogenesis of human T-cell lymphotropic virus type 1 infection.
Phenotypic and functional analysis of γδ T cells in the pathogenesis of human T-cell lymphotropic virus type 1 infection.
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人类T细胞白血病病毒1型(HTLV-1)是严重恶性及炎症性疾病的病因,包括成人T细胞白血病和淋巴瘤以及热带痉挛性截瘫。γδ T细胞在HTLV-1感染中的潜在保护作用尚不清楚。在此,我们证明HTLV-1患者中Vγ9Vδ2 T细胞数量减少,尤其是在伴有HTLV-1相关病理的患者中。这表明γδ T细胞可能参与控制病毒。事实上,我们发现从非感染个体扩增的Vγ9Vδ2 T细胞能够杀伤表达病毒蛋白HBZ和Tax的细胞,而这种表型在美伐他汀存在下被逆转。Vγ9Vδ2 T细胞的细胞毒性不与INF-γ产生的增加相关。与此形成鲜明对比的是,NK细胞的杀伤作用因Tax表达而降低。因此,我们的研究为Vγ9Vδ2 T细胞对HTLV-1感染的潜在保护作用提供了初步证据。利用当前T细胞治疗技术,对这些见解进行治疗性开发是可行的,并可能为预防和治疗HTLV-1相关恶性肿瘤和神经系统并发症提供新工具。
The human T-cell leukemia virus type 1 (HTLV-1) is the cause of serious malignant and inflammatory diseases, including adult T-cell leukemia and lymphoma and tropical spastic paraparesis. The potential protective role of γδ T cells in HTLV-1 infection remains unclear.
Here, demonstrate that there is a decrease in the amount of Vγ9Vδ2 T cells in patients with HTLV-1, especially in those with HTLV-1 associated pathologies. This suggests that γδ T cells could be involved in controlling the virus.
Indeed, we found that Vγ9Vδ2 T cells, expanded from non-infected individuals, can kill cells expressing the viral proteins HBZ and Tax and this phenotype is reversed in the presence of mevastatin. Cytotoxicity by Vγ9Vδ2 T cells was not associated with an increase of INF-γ production. In sharp contrast, killing by NK cells was reduced by Tax expression.
Thus, our study provides initial evidence for a potential protective role of Vγ9Vδ2 T cells against HTLV-1 infection. Therapeutic exploitation of these insights is feasible with current technologies of T-cell therapies and could provide novel tools to prevent and treat HTLV-1-associated malignancies and neurologic complications.
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