CD44 mediates successful interstitial navigation by killer T cells and enables efficient antitumor immunity.
CD44 mediates successful interstitial navigation by killer T cells and enables efficient antitumor immunity.
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DOI：
10.1016/j.immuni.2008.10.015
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发表时间：
2008-12-19
期刊：
影响因子：
32.4
通讯作者：
Weninger, Wolfgang
中科院分区：
文献类型：
--
作者：
Mrass, Paulus;Kinjyo, Ichiko;Ng, Lai Guan;Reiner, Steven L.;Pure, Ellen;Weninger, Wolfgang
杀伤性T淋巴细胞必须在癌组织中寻找并摧毁转化细胞，以消除肿瘤。虽然淋巴细胞是组成性非粘附细胞，但它们在迁移过程中以及在与呈递同源抗原的细胞相互作用时经历兼性极性，这表明淋巴细胞极性可能对肿瘤细胞排斥至关重要。使用肿瘤浸润性T淋巴细胞的双光子成像，我们发现CD44，细胞外基质蛋白和糖胺聚糖的受体，对于肿瘤内的间质导航以及靶细胞筛选的效率至关重要。CD44通过稳定迁移T细胞中的细胞极性而作为肿瘤内运动的关键调节剂发挥作用。稳定的前后不对称性由CD44独立于其胞外结构域维持。相反，迁移极性取决于通过CD44的细胞内结构域向后部细胞突起募集ERM蛋白。这些数据提供的证据表明，由CD44介导的兼性极性是杀伤T细胞迁移和导航的关键调节因子，并且即使是寻找转化细胞的能力的中度干扰也会对最终排斥肿瘤的能力产生深远影响。
A killer T lymphocyte must both seek and destroy transformed cells within cancerous tissue in order to eliminate a tumor. Although lymphocytes are constitutively non-adherent cells, they undergo facultative polarity during migration and upon interaction with cells presenting cognate antigen, suggesting that lymphocyte polarity might be critical for tumor cell rejection. Using two-photon imaging of tumor-infiltrating T lymphocytes, we found that CD44, a receptor for extracellular matrix proteins and glycosaminoglycans, is crucial for interstitial navigation within tumors as well as efficiency of target cell screening. CD44 functions as a critical regulator of intra-tumoral movement by stabilizing cell polarity in migrating T cells. Stable anterior-posterior asymmetry is maintained by CD44 independently of its extracellular domain. Instead, migratory polarity depends on the recruitment of ERM-proteins by the intracellular domain of CD44 to the posterior cellular protrusion. These data provide evidence that facultative polarity mediated by CD44 is a key regulator of killer T cell migration and navigation, and that even moderate disturbances in the ability to seek out transformed cells have profound effects on the capacity to ultimately reject tumors.
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