Expression of leukotriene B₄ receptor-1 on CD8⁺ T cells is required for their migration into tumors to elicit effective antitumor immunity.
Expression of leukotriene B₄ receptor-1 on CD8⁺ T cells is required for their migration into tumors to elicit effective antitumor immunity.
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DOI：
10.4049/jimmunol.1300967
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发表时间：
2013-09-15
期刊：
影响因子：
--
通讯作者：
Haribabu B
中科院分区：
文献类型：
--
作者：
Sharma RK;Chheda Z;Jala VR;Haribabu B
白三烯B4 （LTB4）受体BLT1在多种免疫细胞上表达，并被认为是多种炎症疾病的介质。然而，通过该受体启动的生物反应是否产生促肿瘤炎症或抗肿瘤免疫仍未研究。在这项研究中，我们利用同基因TC-1宫颈癌模型研究了BLT1在抗肿瘤免疫中的作用，并观察到与BLT1+/+小鼠相比，BLT1−/−小鼠的肿瘤生长加快，生存期降低。流式细胞术和共聚焦显微镜对肿瘤浸润的分析显示，BLT1 - / -小鼠肿瘤中效应免疫细胞，尤其是CD8+ t细胞和NK细胞显著减少。基因表达谱证实了BLT1 - / -小鼠肿瘤生长中IFN-γ、颗粒酶- b和IL-2的显著降低。此外，CD8+ T细胞的缺失促进了BLT1+/+小鼠的肿瘤生长，但在BLT1 - / -小鼠中没有。然而，在BLT1+/+和BLT1−/−小鼠的脾脏中观察到相似水平的抗原依赖性CD8+ T细胞介导的杀伤活性。从携带BLT1+/+而非BLT1 - / -小鼠的肿瘤中过继转移CD8+ T细胞可显著降低肿瘤生长并提高Rag2 - / -小鼠的存活率。虽然过继转移的BLT1+/+和BLT1−/−CD8+ T细胞的稳态增殖和其他趋化因子受体的表达谱似乎相似，但BLT1+/+ T淋巴细胞进入肿瘤的数量更多。这些结果表明，BLT1在CD8+ T细胞上的表达在其向肿瘤转运中起着重要作用。
Leukotriene B4 (LTB4) receptor, BLT1 is expressed on variety of immune cells and has been implicated as a mediator of diverse inflammatory diseases. However, whether biological responses initiated via this receptor generate tumor promoting inflammation or anti-tumor immunity remains unexplored. In this study, we investigated the role of BLT1 in antitumor immunity using syngeneic TC-1 cervical cancer model and observed accelerated tumor growth and reduced survival in BLT1−/− mice compared to BLT1+/+ mice. Analysis of the tumor infiltrates by flow cytometry and confocal microscopy revealed a significant decrease in effector immune cells, most notably CD8+-T cells and NK cells in the tumors of the BLT1−/− mice. Gene expression profiling confirmed the dramatic decrease of IFN-γ, granzyme-B and IL-2 in tumors growing in BLT1−/− mice. Furthermore, depletion of CD8+ T cells enhanced the tumor growth in BLT1+/+ but not in BLT1−/− mice. However, similar levels of antigen dependent CD8+ T cell mediated killing activity were observed in spleens of BLT1+/+ and BLT1−/− mice. Adoptive transfer of CD8+ T cells from tumor bearing BLT1+/+ but not BLT1−/− mice significantly reduced tumor growth and increased the survival of Rag2−/− mice. While the homeostatic proliferation and expression profiles of other chemokine receptors of adoptively transferred BLT1+/+ and BLT1−/− CD8+ T cells appears to be similar, BLT1+/+ T-lymphocytes entered the tumors in greater numbers. These results suggest that BLT1 expression on CD8+ T cells plays an important role in their trafficking to tumors.
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DOI：
10.1084/jem.192.3.433
发表时间：
2000-08-07
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Haribabu B;Verghese MW;Steeber DA;Sellars DD;Bock CB;Snyderman R
通讯作者：
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影响因子：
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作者：
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影响因子：
20.3
作者：
Fan, ZS;Yu, P;Fu, YX
通讯作者：
Fu, YX
DOI：
10.1152/ajplung.00212.2005
发表时间：
2006-01-01
影响因子：
4.9
作者：
Medoff, BD;Tager, AM;Luster, AD
通讯作者：
Luster, AD