The contribution of NKT cells, NK cells, and other γ-chain-dependent non-T non-B cells to IL-12-mediated rejection of tumors
The contribution of NKT cells, NK cells, and other γ-chain-dependent non-T non-B cells to IL-12-mediated rejection of tumors
复制标题
DOI：
10.4049/jimmunol.170.3.1197
复制
发表时间：
2003-02-01
影响因子：
4.4
通讯作者：
Carnaud, C
中科院分区：
文献类型：
--
作者：
Park, SH;Kyin, T;Carnaud, C
IL-12是一种有效的细胞因子，可抑制多种肿瘤的生长。在自然条件下以及在治疗条件下的体内。虽然IL-12可以增强许多免疫抗肿瘤机制，包括NK细胞和CTL介导的机制，但最近的报道表明，小鼠CDld限制性的Valpha 14-Jalpha 18 NKT细胞是大多数（如果不是所有）肿瘤排斥模型（包括B16黑色素瘤）中招募的必需细胞类型。在这项研究中，我们已经检查和比较的作用，NKT细胞，T细胞，NK细胞，和其他非T非B细胞在排斥B16黑色素瘤细胞后，外源性管理IL-12。令人惊讶的是，我们的结果未能证实NKT细胞在该模型中的必要作用。相反，我们发现NK细胞介导了对肝转移瘤的排斥反应，而其他γ-依赖性非T非B细胞（可能是淋巴样树突状细胞）是对皮肤肿瘤的排斥反应所必需的。这些发现挑战了IL-12介导的肿瘤排斥反应系统性地需要NKT细胞的观点，而是揭示了根据肿瘤微环境可以招募多种效应途径。
IL-12 is a potent cytokine that impairs the growth of several tumors. in vivo in natural as well as in therapeutic conditions. Although IL-12 can enhance a number of immunological antitumor mechanisms, including those mediated by NK cells and CTL, recent reports have suggested that the mouse CDld-restricted Valpha14-Jalpha18 NKT cell was the essential cell type recruited in most, if not all tumor rejection models, including the B16 melanoma. In this study, we have examined and compared the role of NKT cells, T cells, NK cells, and other non-T non-B cells in the rejection of B16 melanoma cells after exogenous administration of IL-12. Surprisingly, our results failed to confirm a necessary role for NKT cells in this model. Instead, we found that NK cells mediated the rejection of liver metastases, whereas other gammac-dependent non-T non-B cells, possibly lymphoid dendritic cells, were required for rejection of skin tumors. These findings challenge the view that NKT cells are systematically required for IL-12-mediated rejection of tumors, and instead reveal that a variety of effector pathways can be recruited depending on the tumor microenvironment.