調(diào)節(jié)性T細胞（Tregs）通過防止免疫細胞攻擊自身機體對于人體健康有著重要作用,。但是,，在腫瘤微環(huán)境中Tregs細胞卻抑制針對腫瘤細胞的免疫反應。由于Tregs 細胞表面表達CD25,，Rech等人認為針對CD25的單抗免疫抑制藥物daclizumab也許可以清除Tregs 細胞,，從而恢復抗腫瘤免疫反應。
他們的假說得到了證實,。5月16日國際著名轉(zhuǎn)化醫(yī)學雜志Science Translational Medicine發(fā)表了他們的研究論文“CD25 Blockade Depletes and Selectively Reprograms Regulatory T Cells in Concert with Immunotherapy in Cancer Patients”,。
文章報道，daclizumab在體外實驗中可使Tregs 細胞失去免疫抑制和分泌γ干擾素的功能,。這一轉(zhuǎn)變與向效應性T細胞轉(zhuǎn)變的表型一致,。研究者進而給轉(zhuǎn)移性乳腺癌患者同時使用daclizumab和實驗性腫瘤疫苗。結(jié)果發(fā)現(xiàn),，這些患者具有更低的Tregs 細胞數(shù)目和更高水平的疫苗抗原特異性效應T細胞免疫反應,。盡管減少了Tregs 細胞，這些患者并沒有發(fā)生自身免疫反應,。
雖然,，這項研究還處于初級階段，但是daclizumab在不引發(fā)自身免疫的情況下恢復抗腫瘤免疫反應的前景,，仍然備受期待,。(生物谷Bioon.com)
DOI:10.1126/scitranslmed.3003330
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PMID:
CD25 Blockade Depletes and Selectively Reprograms Regulatory T Cells in Concert with Immunotherapy in Cancer Patients
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. Riley,，and Robert H. Vonderheide
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.
