自然杀伤细胞(NK，natural killer cell)是免疫系统中的哨兵，可以快速响应并杀死病变细胞。NK细胞是能针对和消除表面缺乏蛋白MHC I类的细胞，然而许多肿瘤细胞缺少这种蛋白，能抵抗NK细胞的监视和杀伤。
在Journal of Clinical Investigation杂志上的一项新研究显示，细胞因子治疗能增强NK细胞杀伤缺乏MHC I类肿瘤细胞的能力。
利用小鼠模型，加州大学伯克利分校David Raulet确定，缺乏MHC-I类的肿瘤细胞会灭活nk细胞。
由MHC I类阳性肿瘤细胞和MHC I类阴性肿瘤细胞组成的混合瘤也会引起NK细胞变得无响应。重要的是，治疗MHC I类缺陷的肿瘤小鼠，用细胞因子IL-12和IL-18或突变形式的IL-2可恢复NK细胞活性，减少肿瘤大小，并增加小鼠存活。
这项研究的调查结果支持细胞因子治疗或许可用于治疗肿瘤细胞缺乏MHC I类的患者。
原文标题：Cytokine therapy reverses NK Cell anergy in MHC-deficient tumors
原文摘要：Various cytokines have been evaluated as potential anticancer drugs; however, most cytokine trials have shown relatively low efficacy. Here, we found that treatments with IL-12 and IL-18 or with a mutant form of IL-2 (the “superkine” called H9) provided substantial therapeutic benefit for mice specifically bearing MHC class I–deficient tumors, but these treatments were ineffective for mice with matched MHC class I+ tumors. Cytokine efficacy was linked to the reversal of the anergic state of NK cells that specifically occurred in MHC class I–deficient tumors, but not MHC class I+ tumors. NK cell anergy was accompanied by impaired early signal transduction and was locally imparted by the presence of MHC class I–deficient tumor cells, even when such cells were a minor population in a tumor mixture. These results demonstrate that MHC class I–deficient tumor cells can escape from the immune response by functionally inactivating NK cells, and suggest cytokine-based immunotherapy as a potential strategy for MHC class I–deficient tumors. These results suggest that such cytokine therapies would be optimized by stratification of patients. Moreover, our results suggest that such treatments may be highly beneficial in the context of therapies to enhance NK cell functions in cancer patients.
原文地址：http://www.jci.org/articles/view/74337 DOI：10.1172/JCI74337
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