Eradication of metastatic renal cell carcinoma after adenovirus-encoded TNF-related apoptosis-inducing ligand (TRAIL)/CpG immunotherapy.
Eradication of metastatic renal cell carcinoma after adenovirus-encoded TNF-related apoptosis-inducing ligand (TRAIL)/CpG immunotherapy.
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DOI：
10.1371/journal.pone.0031085
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Griffith TS
中科院分区：
文献类型：
--
作者：
Norian LA;Kresowik TP;Rosevear HM;James BR;Rosean TR;Lightfoot AJ;Kucaba TA;Schwarz C;Weydert CJ;Henry MD;Griffith TS
尽管有证据表明抗肿瘤免疫对肾细胞癌（RCC）有保护作用，但很少有患者对免疫治疗有客观反应，而且一旦发生转移，这种疾病是致命的。我们询问在原发肿瘤部位给予腺病毒编码的小鼠tnf相关凋亡诱导配体（Ad5mTRAIL）和CpG寡核苷酸的组合免疫治疗在多大程度上可以证明对转移性小鼠RCC有效。为了量化小鼠原发性肾和转移性肿瘤的生长，我们建立了表达荧光素酶的Renca细胞系，并通过生物发光成像监测肿瘤负荷。原位肿瘤侵袭引起侵袭性原发肿瘤和肺转移，在第7天可检测到。第7天肾内给药Ad5mTRAIL+CpG导致效应表型CD4和CD8 T细胞在第12天涌入肾脏，并使已建立的原发性肾肿瘤消退。肾内免疫治疗还导致全身免疫反应，其特征是脾肿大，血清IgG水平升高，CD4和CD8 T细胞浸润增加，肺部转移性肿瘤消除。肿瘤消退主要依赖于CD8 T细胞，并导致治疗小鼠的存活时间延长。因此，在原发肿瘤部位局部给药Ad5mTRAIL+CpG可启动cd8依赖性全身免疫，足以引起转移性肺肿瘤的消退。类似的方法可能对转移性肾细胞癌患者有益。
Despite evidence that antitumor immunity can be protective against renal cell carcinoma (RCC), few patients respond objectively to immunotherapy and the disease is fatal once metastases develop. We asked to what extent combinatorial immunotherapy with Adenovirus-encoded murine TNF-related apoptosis-inducing ligand (Ad5mTRAIL) plus CpG oligonucleotide, given at the primary tumor site, would prove efficacious against metastatic murine RCC. To quantitate primary renal and metastatic tumor growth in mice, we developed a luciferase-expressing Renca cell line, and monitored tumor burdens via bioluminescent imaging. Orthotopic tumor challenge gave rise to aggressive primary tumors and lung metastases that were detectable by day 7. Intra-renal administration of Ad5mTRAIL+CpG on day 7 led to an influx of effector phenotype CD4 and CD8 T cells into the kidney by day 12 and regression of established primary renal tumors. Intra-renal immunotherapy also led to systemic immune responses characterized by splenomegaly, elevated serum IgG levels, increased CD4 and CD8 T cell infiltration into the lungs, and elimination of metastatic lung tumors. Tumor regression was primarily dependent upon CD8 T cells and resulted in prolonged survival of treated mice. Thus, local administration of Ad5mTRAIL+CpG at the primary tumor site can initiate CD8-dependent systemic immunity that is sufficient to cause regression of metastatic lung tumors. A similar approach may prove beneficial for patients with metastatic RCC.
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影响因子：
45.3
作者：
FYFE, G;FISHER, RI;LOUIE, AC
通讯作者：
LOUIE, AC
影响因子：
6.2
作者：
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通讯作者：
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影响因子：
5
作者：
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影响因子：
4
作者：
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通讯作者：
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影响因子：
3.1
作者：
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通讯作者：
Xiong, Sidong