Dongnam Institute of Radiological and Medical Sciences, Busan, Korea; Department of Biochemistry, Pusan National University School of Medicine, Yangsan, Korea.
Department of Biochemistry, Pusan National University School of Medicine, Yangsan, Korea.
Int J Radiat Oncol Biol Phys. 2015 Jun 1;92(2):390-8. doi: 10.1016/j.ijrobp.2015.01.011. Epub 2015 Mar 5.
To investigate the potential of low-dose cyclophosphamide (LD-CTX) and anti-CD25 antibody to prevent activation of regulatory T cells (Tregs) during radiation therapy.
We used LD-CTX and anti-CD25 monoclonal antibody as a means to inhibit Tregs and improve the therapeutic effect of radiation in a mouse model of lung and colon cancer. Mice were irradiated on the tumor mass of the right leg and treated with LD-CTX and anti-CD25 antibody once per week for 3 weeks.
Combined treatment of LD-CTX or anti-CD25 antibody with radiation significantly decreased Tregs in the spleen and tumor compared with control and irradiation only in both lung and colon cancer. Combinatorial treatments resulted in a significant increase in the effector T cells, longer survival rate, and suppressed irradiated and distal nonirradiated tumor growth. Specifically, the combinatorial treatment of LD-CTX with radiation resulted in outstanding regression of local and distant tumors in colon cancer, and almost all mice in this group survived until the end of the study.
Our results suggest that Treg depletion strategies may enhance radiation-mediated antitumor immunity and further improve outcomes after radiation therapy.
研究低剂量环磷酰胺（LD-CTX）和抗 CD25 抗体在放射治疗过程中预防调节性 T 细胞（Tregs）激活的潜力。
我们使用 LD-CTX 和抗 CD25 单克隆抗体作为抑制 Tregs 的手段，并在肺癌和结肠癌的小鼠模型中提高放射治疗的疗效。在右腿肿瘤上照射小鼠，并每周用 LD-CTX 和抗 CD25 抗体治疗一次，共 3 周。
与对照组和仅照射组相比，LD-CTX 或抗 CD25 抗体联合放射治疗显著降低了肺癌和结肠癌脾脏和肿瘤中的 Tregs。联合治疗导致效应 T 细胞显著增加，生存率提高，并抑制了照射和远端未照射肿瘤的生长。具体来说，LD-CTX 联合放射治疗导致结肠癌局部和远处肿瘤的显著消退，该组几乎所有小鼠都存活到研究结束。
我们的结果表明，Treg 耗竭策略可能增强放射介导的抗肿瘤免疫，并进一步改善放射治疗后的疗效。
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