Expression of NF-κB p50 in tumor stroma limits the control of tumors by radiation therapy.
Expression of NF-κB p50 in tumor stroma limits the control of tumors by radiation therapy.
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DOI：
10.1371/journal.pone.0039295
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Gough MJ
中科院分区：
文献类型：
--
作者：
Crittenden MR;Cottam B;Savage T;Nguyen C;Newell P;Gough MJ
放射疗法旨在以最小的正常组织毒性杀死癌细胞。死亡的癌细胞被认为是肿瘤抗原的来源，并可能释放内源性免疫佐剂到肿瘤环境中。由于这些原因，放射治疗可能是一种有效的方式来启动新的抗肿瘤适应性免疫反应，可以针对残留疾病和远处转移。然而，肿瘤产生了一个由M2分化的肿瘤巨噬细胞主导的环境，支持肿瘤侵袭、转移和逃避免疫控制。在这项研究中，我们证明在小鼠肿瘤放射治疗后，肿瘤巨噬细胞大量涌入，最终极化为免疫抑制。我们通过体外模型证明，这种极化是由NFκB p50的转录调节介导的，并且在缺乏NFκB p50的小鼠中，放射治疗更有效。我们认为，尽管有机会增加抗原特异性适应性免疫反应，但放射治疗后的内在修复过程可能限制了控制残留疾病的能力。
Radiation therapy aims to kill cancer cells with a minimum of normal tissue toxicity. Dying cancer cells have been proposed to be a source of tumor antigens and may release endogenous immune adjuvants into the tumor environment. For these reasons, radiation therapy may be an effective modality to initiate new anti-tumor adaptive immune responses that can target residual disease and distant metastases. However, tumors engender an environment dominated by M2 differentiated tumor macrophages that support tumor invasion, metastases and escape from immune control. In this study, we demonstrate that following radiation therapy of tumors in mice, there is an influx of tumor macrophages that ultimately polarize towards immune suppression. We demonstrate using in vitro models that this polarization is mediated by transcriptional regulation by NFκB p50, and that in mice lacking NFκB p50, radiation therapy is more effective. We propose that despite the opportunity for increased antigen-specific adaptive immune responses, the intrinsic processes of repair following radiation therapy may limit the ability to control residual disease.
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影响因子：
15.9
作者：
Fadok, VA;Bratton, DL;Henson, PM
通讯作者：
Henson, PM
影响因子：
6.6
作者：
Lin, Elaine Y.;Li, Jiu-feng;Pollard, Jeffrey W.
通讯作者：
Pollard, Jeffrey W.
DOI：
10.1097/cji.0b013e3181ee7095
发表时间：
2010-10
期刊：
Journal of immunotherapy (Hagerstown, Md. : 1997)
影响因子：
--
作者：
Gough MJ;Crittenden MR;Sarff M;Pang P;Seung SK;Vetto JT;Hu HM;Redmond WL;Holland J;Weinberg AD
通讯作者：
Weinberg AD
用激动性抗GITR mAb治疗晚期肿瘤及其对肿瘤浸润Foxp3+CD25+CD4+调节T细胞的影响。
影响因子：
15.3
作者：
Ko, K;Yamazaki, S;Nakamura, K;Nishioka, T;Hirota, K;Yamaguchi, T;Shimizu, J;Nomura, T;Chiba, T;Sakaguchi, S
通讯作者：
Sakaguchi, S
DOI：
10.1073/pnas.0911378107
发表时间：
2010-05-04
影响因子：
11.1
作者：
Ahn, G-One;Tseng, Diane;Brown, J. Martin
通讯作者：
Brown, J. Martin