肿瘤细胞治疗研究
英文原题：Ex vivo expansion and activation of Vγ9Vδ2 T cells by CELMoDs in combination with zoledronic acid.
Ex vivo expansion and activation of Vγ9Vδ2 T cells by CELMoDs in combination with zoledronic acid.
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随着多发性骨髓瘤（MM）的进展，免疫效应细胞数量和功能下降并变得耗竭。这仍然是一个不可逾越的临床问题，必须通过开发新的方法来重振抗MM免疫。人Vγ9Vδ2 T（Vδ2 + γδ T）细胞作为抵御病原体和肿瘤的第一道防线，在氨基双膦酸盐联合IL-2处理下可从外周血单个核细胞（PBMCs）中体外扩增。
在此，我们证明，下一代免疫调节剂——cereblon E3连接酶调节剂（CELMoDs），以及来那度胺和泊马度胺，在唑来膦酸（ZA）存在下可从PBMCs中扩增Th1样Vδ2 + γδ T细胞。
然而，尽管PBMCs中诱导了IL-2产生，这些免疫调节药物对Th1样Vδ2 + γδ T细胞的扩增在IL-2阻断下被消除。BTN3A1触发磷酸抗原呈递给γδ T细胞受体，是γδ T细胞扩增和活化所必需的。ZA而非这些免疫调节药物上调单核细胞中的BTN3A1。这些结果表明，免疫调节药物和ZA在Th1样Vδ2 + γδ T细胞扩增中具有协同作用，并为人类Vδ2 + γδ T细胞作为效应细胞的临床应用提供了重要知识。
As multiple myeloma (MM) progresses, immune effector cells decrease in number and function and become exhausted. This remains an insurmountable clinical issue that must be addressed by development of novel modalities to revitalize anti-MM immunity. Human Vγ9Vδ2 T (Vδ2 + γδ T) cells serve as the first line of defense against pathogens as well as tumors and can be expanded ex vivo from peripheral blood mononuclear cells (PBMCs) upon treatment with amino-bisphosphonates in combination with IL-2.
Here, we demonstrated that next-generation immunomodulators called cereblon E3 ligase modulators (CELMoDs), as well as lenalidomide and pomalidomide, expanded Th1-like Vδ2 + γδ T cells from PBMCs in the presence of zoledronic acid (ZA).
However, the expansion of Th1-like Vδ2 + γδ T cells by these immunomodulatory drugs was abolished under IL-2 blockade, although IL-2 production was induced in PBMCs. BTN3A1 triggers phosphoantigen presentation to γδ T-cell receptors and is required for γδ T-cell expansion and activation.
ZA but not these immunomodulatory drugs upregulated BTN3A1 in monocytes. These results suggest that immunomodulatory drugs and ZA have cooperative roles in expansion of Th1-like Vδ2 + γδ T cells, and provide the important knowledge for clinical application of human Vδ2 + γδ T cells as effector cells.
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