The yin and yang of leukotriene B(4) mediated inflammation in cancer.

The yin and yang of leukotriene B(4) mediated inflammation in cancer.
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DOI:
10.1016/j.smim.2017.09.005
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发表时间:
2017-10
影响因子:
7.8
通讯作者:
Haribabu B
Haribabu B
中科院分区:
医学2区
文献类型:
--
作者:
Jala VR;Bodduluri SR;Satpathy SR;Chheda Z;Sharma RK;Haribabu B

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高亲和力的白三烯B4受体BLT 1介导不同白细胞亚群对感染或炎症部位的趋化性。尽管LTB 4/BLT 1轴在过敏、自身免疫和心血管疾病中的病理功能已经得到了很好的确立,但它在癌症中的作用才刚刚开始显现。在这篇综述中,我们总结了LTB 4/BLT 1轴的最新研究结果,使不同的结果对肿瘤进展。在硅肺诱导的炎症促进的小鼠肺肿瘤模型中,BLT 1的基因缺失减弱了嗜酸性炎症和肿瘤促进。相比之下,在肠肿瘤发生的自发模型中,BLT 1的缺乏导致有缺陷的粘膜宿主反应、改变的微生物群和细菌依赖性结肠肿瘤进展。此外,BLT 1介导的CD 8 + T细胞募集被证明是在许多异种移植模型中启动抗肿瘤免疫所必需的,并且对于有效的基于PD 1的免疫疗法至关重要。BLT 2介导的化疗耐药性,肿瘤促进和转移也进行了讨论。这一新的信息指出了我们对癌症中LTB 4通路的理解的范式转变。
The high affinity leukotriene B4 receptor, BLT1 mediates chemotaxis of diverse leukocyte subsets to the sites of infection or inflammation. Whereas the pathological functions of LTB4/BLT1 axis in allergy, autoimmunity and cardiovascular disorders are well established; its role in cancer is only beginning to emerge. In this review, we summarize recent findings on LTB4/BLT1 axis enabling distinct outcomes toward tumor progression. In a mouse lung tumor model promoted by silicosis-induced inflammation, genetic deletion of BLT1 attenuated neutrophilic inflammation and tumor promotion. In contrast, in a spontaneous model of intestinal tumorigenesis, absence of BLT1 led to defective mucosal host response, altered microbiota and bacteria dependent colon tumor progression. Furthermore, BLT1 mediated CD8+ T cell recruitment was shown to be essential for initiating anti-tumor immunity in number of xenograft models and is critical for effective PD1 based immunotherapy. BLT2 mediated chemotherapy resistance, tumor promotion and metastasis are also discussed. This new information points to a paradigm shift in our understanding of the LTB4 pathways in cancer.
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