自然殺傷細(xì)胞(NK，natural killer cell)是免疫系統(tǒng)中的哨兵，可以快速響應(yīng)并殺死病變細(xì)胞。NK細(xì)胞是能針對和消除表面缺乏蛋白MHC I類的細(xì)胞，然而許多腫瘤細(xì)胞缺少這種蛋白，能抵抗NK細(xì)胞的監(jiān)視和殺傷。
在Journal of Clinical Investigation雜志上的一項新研究顯示，細(xì)胞因子治療能增強(qiáng)NK細(xì)胞殺傷缺乏MHC I類腫瘤細(xì)胞的能力。
利用小鼠模型，加州大學(xué)伯克利分校David Raulet確定，缺乏MHC-I類的腫瘤細(xì)胞會滅活nk細(xì)胞。
由MHC I類陽性腫瘤細(xì)胞和MHC I類陰性腫瘤細(xì)胞組成的混合瘤也會引起NK細(xì)胞變得無響應(yīng)。重要的是，治療MHC I類缺陷的腫瘤小鼠，用細(xì)胞因子IL-12和IL-18或突變形式的IL-2可恢復(fù)NK細(xì)胞活性，減少腫瘤大小，并增加小鼠存活。
這項研究的調(diào)查結(jié)果支持細(xì)胞因子治療或許可用于治療腫瘤細(xì)胞缺乏MHC I類的患者。
原文標(biāo)題：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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