肿瘤细胞治疗研究
英文原题：TGF-β1 potentiates Vγ9Vδ2 T cell adoptive immunotherapy of cancer.
尽管γδ T细胞在肿瘤监视中发挥作用，但过继性免疫治疗使用γδ T细胞的疗效有限。
尽管γδ T细胞在肿瘤监视中发挥作用，但过继性免疫治疗使用γδ T细胞的疗效有限。为增强向骨髓的迁移，循环Vγ9Vδ2 T细胞在含TGF-β1和IL-2的无血清培养基中扩增（γδ[T2]细胞），或在仅含IL-2的培养基中扩增（γδ[2]细胞，作为对照）。出乎意料的是，与γδ[2]对照相比，TGF-β1还增加了γδ[T2]细胞的产量和活力。γδ[T2]细胞分化程度较低，但在几种白血病和实体瘤模型中显示出增强的溶细胞活性、细胞因子释放和抗肿瘤活性。通过使用氨基双膦酸盐或Ara-C致敏癌细胞，疗效进一步增强。描述了TGF-β的若干贡献效应，包括前列腺素E2受体下调、TGF-β不敏感性和整合素活性上调。在急性髓系白血病（AML）中鉴定出有利的γδ[T2]特征，支持了其生物学相关性。鉴于其增强的治疗活性和与异体使用的兼容性，γδ[T2]细胞值得在癌症免疫治疗中进行评估。
Despite its role in cancer surveillance, adoptive immunotherapy using γδ T cells has achieved limited efficacy. To enhance trafficking to bone marrow, circulating Vγ9Vδ2 T cells are expanded in serum-free medium containing TGF-β1 and IL-2 (γδ[T2] cells) or medium containing IL-2 alone (γδ[2] cells, as the control). Unexpectedly, the yield and viability of γδ[T2] cells are also increased by TGF-β1, when compared to γδ[2] controls. γδ[T2] cells are less differentiated and yet display increased cytolytic activity, cytokine release, and antitumor activity in several leukemic and solid tumor models. Efficacy is further enhanced by cancer cell sensitization using aminobisphosphonates or Ara-C. A number of contributory effects of TGF-β are described, including prostaglandin E 2 receptor downmodulation, TGF-β insensitivity, and upregulated integrin activity. Biological relevance is supported by the identification of a favorable γδ[T2] signature in acute myeloid leukemia (AML). Given their enhanced therapeutic activity and compatibility with allogeneic use, γδ[T2] cells warrant evaluation in cancer immunotherapy.
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