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Sci Transl Med:daclizumab调控调节性T细胞促进肿瘤免疫治疗

调节性T细胞(Tregs)通过防止免疫细胞攻击自身机体对于人体健康有着重要作用。但是,在肿瘤微环境中Tregs细胞却抑制针对肿瘤细胞的免疫反应。由于Tregs 细胞表面表达CD25,Rech等人认为针对CD25的单抗免疫抑制药物daclizumab也许可以清除Tregs 细胞,从而恢复抗肿瘤免疫反应。

他们的假说得到了证实。5月16日国际著名转化医学杂志Science Translational Medicine发表了他们的研究论文“CD25 Blockade Depletes and Selectively Reprograms Regulatory T Cells in Concert with Immunotherapy in Cancer Patients”。

文章报道,daclizumab在体外实验中可使Tregs 细胞失去免疫抑制和分泌γ干扰素的功能。这一转变与向效应性T细胞转变的表型一致。研究者进而给转移性乳腺癌患者同时使用daclizumab和实验性肿瘤疫苗。结果发现,这些患者具有更低的Tregs 细胞数目和更高水平的疫苗抗原特异性效应T细胞免疫反应。尽管减少了Tregs 细胞,这些患者并没有发生自身免疫反应。

虽然,这项研究还处于初级阶段,但是daclizumab在不引发自身免疫的情况下恢复抗肿瘤免疫反应的前景,仍然备受期待。(生物谷Bioon.com)


参考文献:


CD25 Blockade Depletes and Selectively Reprograms Regulatory T Cells in Concert with Immunotherapy in Cancer Patients

DOI:
AUTHORS:Andrew J.Rech, Rosemarie Mick, Sunil Martin1, Adri Recio, Nicole A. Aqui, Daniel J. Powell Jr., Theresa A. Colligon1, Jennifer A. Trosko1, Leah I. Leinbach, Charles H. Pletcher, Carol K. Tweed, Angela DeMichele, Kevin R. Fox, Susan M. Domchek, James L. Ri
ABSTRACT:Regulatory T cells (Tregs) are key mediators of immune tolerance and feature prominently in cancer. Depletion of CD25+ FoxP3+ Tregs in vivo may promote T cell cancer immunosurveillance, but no strategy to do so in humans while preserving immunity and preventing autoimmunity has been validated. We evaluated the Food and Drug Administration–approved CD25-blocking monoclonal antibody daclizumab with regard to human Treg survival and function. In vitro, daclizumab did not mediate antibody-dependent or complement-mediated cytotoxicity but rather resulted in the down-regulation of FoxP3 selectively among CD25high CD45RAneg Tregs. Moreover, daclizumab-treated CD45RAneg Tregs lost suppressive function and regained the ability to produce interferon-γ, consistent with reprogramming. To understand the impact of daclizumab on Tregs in vivo, we performed a clinical trial of daclizumab in combination with an experimental cancer vaccine in patients with metastatic breast cancer. Daclizumab administration led to a marked and prolonged decrease in Tregs in patients. Robust CD8 and CD4 T cell priming and boosting to all vaccine antigens were observed in the absence of autoimmunity. We conclude that CD25 blockade depletes and selectively reprograms Tregs in concert with active immune therapy in cancer patients. These results suggest a mechanism to target cancer-associated Tregs while avoiding autoimmunity.

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