Densely granulated murine NK cells eradicate large solid tumors.
Densely granulated murine NK cells eradicate large solid tumors.
复制标题
DOI：
10.1158/0008-5472.can-11-3208
复制
发表时间：
2012-04-15
期刊：
影响因子：
11.2
通讯作者：
Schreiber H
中科院分区：
文献类型：
--
作者：
Liu RB;Engels B;Arina A;Schreiber K;Hyjek E;Schietinger A;Binder DC;Butz E;Krausz T;Rowley DA;Jabri B;Schreiber H
NK细胞抑制肿瘤形成、复发和转移的早期阶段。在这里，我们表明NK细胞也可以根除大型实体瘤。根除依赖于由于肿瘤微环境中的癌细胞释放和呈递的IL 15导致的增殖NK细胞的大量浸润。浸润的NK细胞具有明显的形态学特征，即密集负载PAS阳性、抗淀粉酶颗粒，类似于子宫NK细胞。穿孔素介导的这些密集颗粒状NK细胞的杀伤对于肿瘤根除至关重要。IL 15受体α在癌细胞上的表达是有效诱导颗粒状NK细胞所必需的，而在宿主基质细胞上的表达是防止肿瘤在几乎完全破坏后复发所必需的。这些结果表明，在癌症部位释放的IL 15诱导高度活化的NK细胞，导致大实体瘤的根除。
NK cells inhibit early stages of tumor formation, recurrence and metastasis. Here we show that NK cells can also eradicate large solid tumors. Eradication depended on the massive infiltration of proliferating NK cells due to IL15 released and presented by the cancer cells in the tumor microenvironment. Infiltrating NK cells had the striking morphological feature of being densely loaded with PAS-positive, diastase-resistant granules, resembling uterine NK cells. Perforin-mediated killing by these densely granulated NK cells was essential for tumor eradication. Expression of the IL15 receptor α on cancer cells was needed to efficiently induce granulated NK cells and expression on host stromal cells was essential to prevent tumor relapse after near complete destruction. These results indicate that IL15 released at the cancer site induces highly activated NK cells that lead to eradication of large solid tumors.