Committee on Immunology, Department of Pathology, The University of Chicago, Chicago, Illinois 60637, USA.
Cancer Res. 2012 Apr 15;72(8):1964-74. doi: 10.1158/0008-5472.CAN-11-3208. Epub 2012 Feb 28.
Natural killer (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 interleukin 15 (IL-15) released and presented by the cancer cells in the tumor microenvironment. Infiltrating NK cells had the striking morphologic feature of being densely loaded with periodic acid-Schiff-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 IL-15 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 IL-15 released at the cancer site induces highly activated NK cells that lead to eradication of large solid tumors.
自然杀伤 (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。根除取决于由于癌细胞在肿瘤微环境中释放和呈递的白细胞介素 15 (IL-15) 而导致大量增殖的 NK 细胞的浸润。浸润的 NK 细胞具有一个显著的形态特征，即密集装载过碘酸-Schiff 阳性、耐淀粉酶颗粒，类似于子宫 NK 细胞。这些颗粒密集的 NK 细胞通过穿孔素介导的杀伤对于肿瘤根除至关重要。癌细胞上表达白细胞介素 15 受体 α 对于有效诱导颗粒状 NK 细胞是必要的，而表达在宿主基质细胞上对于防止肿瘤在几乎完全破坏后复发是必要的。这些结果表明，在肿瘤部位释放的白细胞介素 15 诱导高度激活的 NK 细胞，从而导致大型实体瘤的根除。
