Therapeutic effects of ablative radiation on local tumor require CD8+ T cells: changing strategies for cancer treatment
Therapeutic effects of ablative radiation on local tumor require CD8+ T cells: changing strategies for cancer treatment
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DOI：
10.1182/blood-2009-02-206870
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发表时间：
2009-07-16
期刊：
影响因子：
20.3
通讯作者：
Fu, Yang-Xin
中科院分区：
文献类型：
--
作者：
Lee, Youjin;Auh, Sogyong L.;Fu, Yang-Xin
局部晚期癌症或远处转移的患者经常接受化疗和/或分次放疗（RT）的长期治疗。尽管最初的临床反应，但这些患者经常出现治疗耐药性，治愈罕见。放射治疗技术的发展允许使用高剂量（或消融）放射治疗靶向局部肿瘤，对周围正常组织的损害有限。我们报道，消融放疗后肿瘤负荷的减少主要取决于t细胞反应。消融性放疗显著增加引流淋巴组织中的T细胞启动，以CD8(+) T细胞依赖的方式减少/根除原发肿瘤或远处转移。我们进一步证明，消融性RT引发的免疫反应和肿瘤减少被传统的分割RT或辅助化疗所消除，但被局部免疫治疗大大增强。我们的研究挑战了当前放疗/化疗策略的基本原理，并强调了免疫激活在预防肿瘤复发中的重要性。我们的发现强调需要新的策略，不仅减少肿瘤负担，而且增强抗肿瘤免疫的作用。（《血液》，2009;114:589-595）
Patients with locally advanced cancer or distant metastasis frequently receive prolonged treatment with chemotherapy and/or fractionated radiotherapy (RT). Despite the initial clinical response, treatment resistance frequently develops and cure in these patients is uncommon. Developments in RT technology allow for the use of high-dose (or ablative) RT to target local tumors, with limited damage to the surrounding normal tissue. We report that reduction of tumor burden after ablative RT depends largely on T-cell responses. Ablative RT dramatically increases T-cell priming in draining lymphoid tissues, leading to reduction/eradication of the primary tumor or distant metastasis in a CD8(+) T cell-dependent fashion. We further demonstrate that ablative RT-initiated immune responses and tumor reduction are abrogated by conventional fractionated RT or adjuvant chemotherapy but greatly amplified by local immunotherapy. Our study challenges the rationale for current RT/chemotherapy strategies and highlights the importance of immune activation in preventing tumor relapse. Our findings emphasize the need for new strategies that not only reduce tumor burden but also enhance the role of antitumor immunity. (Blood. 2009; 114:589-595)