Expression of Arginase I in Myeloid Cells Limits Control of Residual Disease after Radiation Therapy of Tumors in Mice
Expression of Arginase I in Myeloid Cells Limits Control of Residual Disease after Radiation Therapy of Tumors in Mice
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DOI：
10.1667/rr13493.1
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发表时间：
2014-08-01
影响因子：
3.4
通讯作者：
Gough, Michael J.
中科院分区：
文献类型：
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作者：
Crittenden, Marka R.;Savage, Talicia;Gough, Michael J.
越来越多的证据表明，放射治疗可以产生有助于肿瘤控制的适应性免疫反应。然而，在缺乏额外免疫治疗的情况下，适应性免疫反应不足以预防肿瘤复发或影响远处疾病。多种模型表明，肿瘤浸润的髓样细胞表现出不同的活化表型，能够抑制适应性免疫反应，最近的数据表明，用细胞毒性疗法治疗的肿瘤中的髓样反应限制了肿瘤的控制。我们假设肿瘤髓系细胞通过表达精氨酸酶I抑制放射治疗后的适应性免疫反应。在小鼠中使用髓系细胞特异性缺失精氨酸酶I，我们证明放射治疗后肿瘤控制得到改善。然而，尽管有条件地敲低精氨酸酶i，肿瘤仍会复发。由于多种替代因素可能联合抑制适应性免疫，我们提出靶向巨噬细胞分化可能是比靶向单个抑制途径更有效的策略。(C) 2014年由辐射研究学会出版
An accumulating body of evidence demonstrates that radiation therapy can generate adaptive immune responses that contribute to tumor control. However, in the absence of additional immune therapy, the adaptive immune response is insufficient to prevent tumor recurrence or affect distant disease. It has been shown in multiple models that tumor-infiltrating myeloid cells exhibit alternative activation phenotypes and are able to suppress adaptive immune responses, and recent data suggests that the myeloid response in tumors treated with cytotoxic therapy limits tumor control. We hypothesized that tumor myeloid cells inhibit the adaptive immune response after radiation therapy through expression of the enzyme arginase I. Using a myeloid cell-specific deletion of arginase I in mice, we demonstrate an improved tumor control after radiation therapy. However, tumors still recurred despite the conditional knockdown of arginase I. Since multiple alternative factors may combine to inhibit adaptive immunity, we propose that targeting macrophage differentiation may be a more effective strategy than targeting individual suppressive pathways. (C) 2014 by Radiation Research Society