Classic versus non‐classic: A survival Kit for life in the skin
Classic versus non‐classic: A survival Kit for life in the skin
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经典与非经典：皮肤生命的生存套件
DOI：
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发表时间：
2009
影响因子：
4.3
通讯作者：
Hiroaki Yamamoto
中科院分区：
文献类型：
--
作者：
Shigeyuki Uehara;Akiha Kawasaki;Hiroaki Yamamoto
和caspase上调。使用可移植肿瘤和自发性黑色素瘤的遗传小鼠模型，Tormo等人还表明，MDA-5依赖性poly I：C <$PEI诱导的抗肿瘤作用可以在体内证明，并且不需要T和B细胞或自然杀伤（NK）细胞的细胞毒性功能。这些数据强烈表明对肿瘤而不是免疫细胞的直接影响，尽管不能排除NK细胞的其他先天抗性机制和非细胞毒性功能。这让人想起在乳腺癌的旧临床试验中聚A：U（TLR 3的强配体，但不是胞质MDA-5或RIG-I的强配体）的抗肿瘤作用，其中最近发现治疗结果与肿瘤细胞上的TLR 3表达相关，因此表明直接的肿瘤细胞毒性而不是通过TLR 3触发炎症细胞的免疫刺激作用（Salaun et al.，2007年）。尽管Tormo等人的数据强调了配制的聚I：C直接诱导黑色素瘤细胞死亡的能力，但在临床环境中靶向RNA传感器不太可能完全成功，除非细胞死亡与免疫原性增加和抗原特异性免疫应答的诱导相关。在自噬期间将抗原货物递送到细胞质中已被建议促进II类和可能I类MHC的肿瘤抗原呈递。poly I：C <$PEI治疗很可能引发免疫原性细胞死亡，因此除了其直接的细胞毒性作用外，还可能诱导垂死的黑素瘤细胞增加抗原呈递和DC呈递肿瘤抗原，在免疫活性宿主中可能引发保护性抗肿瘤CD 4和CD 8 T细胞介导的免疫应答。总之，Tormo等人的论文提出了一些意想不到的新发现，这些发现将自噬、MDA-5活化和在体外和体内用PEI复合的poly I：C处理诱导的黑素瘤细胞凋亡联系起来。这些数据将迫使我们重新评估一些早期的研究在体内抗肿瘤作用的分子机制的poly I：C和设计成功的治疗性抗肿瘤干预使用dsRNA模拟化合物具有重要意义。
and caspase up-regulation. Using both transplantable tumors and genetic mouse models of spontaneous melanoma, Tormo et al. also show that the MDA-5-dependent poly I:C ⁄ PEIinduced anti-tumor effect can be demonstrated in vivo and it does not require T and B cells or the cytotoxic functions of natural killer (NK) cells. These data strongly suggest a direct effect on the tumor rather than immune cells, although other innate resistance mechanisms and non-cytotoxic functions of NK cells cannot be excluded. This is reminiscent of the anti-tumor effect of poly A:U (a powerful ligand for TLR3 but not for cytosolic MDA-5 or RIG-I) in old clinical trials of breast cancer in which the therapeutic results were recently found to correlate with TLR3 expression on tumor cells, thus suggesting direct tumor cytotoxicity rather than an immunostimulatory effect through TLR3 triggering on inflammatory cells (Salaun et al., 2007). Although the data by Tormo et al. stress the ability of formulated poly I:C to directly induce melanoma cell death, targeting RNA sensors in a clinical setting is unlikely to be fully successful unless cell death is associated with increased immunogenicity and induction of an antigen-specific immune response. Delivery of antigenic cargo into the cytoplasm during autophagy has been suggested to promote tumor antigen presentation for class II and probably class I MHC. It is likely that poly I:C ⁄ PEI treatment triggers immunogenic cell death, hence in addition to its direct cytotoxic effect it is possibly also inducing increased antigen presentation by the dying melanoma cells and presentation of tumor antigens by DCs that in immunocompetent hosts may elicit protective anti-tumor CD4 and CD8 T cell-mediated immune responses. In conclusion, the paper by Tormo et al. presents some unexpected new findings linking autophagy, MDA-5 activation and apoptosis of melanoma cells induced by treatment with PEI-complexed poly I:C both in vitro and in vivo. These data will force us to reevaluate some of the earlier studies on the molecular mechanisms of in vivo anti-tumor effect of poly I:C and have important implications for designing successful therapeutic anti-tumor interventions using dsRNA mimetic compounds.
受体酪氨酸激酶依赖性神经嵴迁移响应差异局部生长因子。
DOI：
10.1002/bies.950190411
发表时间：
1997
期刊：
BioEssays : news and reviews in molecular, cellular and developmental biology.
影响因子：
--
作者：
Wehrle-Haller,B;Weston,JA
通讯作者：
Weston,JA
影响因子：
7.3
作者：
Kelsh RN;Harris ML;Colanesi S;Erickson CA
通讯作者：
Erickson CA