基于NK细胞的肿瘤免疫治疗研究进展

Progress in NK cell-based immunotherapy of tumor

NK细胞发育分化研究取得较大进展,除骨髓、外周血和脾脏外,胸腺、肝脏、淋巴结等器官中NK细胞前体细胞(NK precursors,NKPs)的分化及其迁移特性引起极大关注。人类CD56brightNK细胞易于在次级淋巴组织及非淋巴组织中聚集,而CD56d imNK细胞则能够趋化招募至外周炎症部位。NK细胞活化受体包括细胞因子受体、膜整合素分子、天然细胞毒受体、免疫球蛋白样杀伤受体,以及新发现的许多识别分子。在肿瘤的发生发展过程中,NK细胞既可以通过"内识别"方式直接识别恶性转化的癌细胞并被活化,也可以在辅助细胞(单核细胞、巨噬细胞、树突状细胞)的作用下被活化。DC细胞可以触发NK细胞的活化,其中IL-15R-IL-15的反式信号转导极其重要。NK细胞的肿瘤生物治疗取得了较大进展,其中基于NK细胞天然免疫识别的肿瘤生物治疗有很多新的途径。

The development and differentiation of NK cells are highly noted in recent years. In addition to the peripheral blood, spleen and bone marrow, the liver, lymph nodes and thymus are also considered as important organs for differentiation of NK cell precursors （NKPs） . Human NK cell subset CD56bright is enriched in secondary lymphoid tissues and non-lymph tissues; NK subset cell CD56dim can migrate to peripheral inflammatory region. Activating receptors on NK cells include cytokine receptors, integrin receptors, natural cytotoxic receptors, immunoglobulin-like killer receptors, and many new receptors and ligands different from the aforementioned receptor families. In the process of tumor progression, NK cells can directly recognize malignant cells via ＂internal recognition＂ and be activated; they can also be activated by accessory cells such as monocytes, maerophages and dentritic cells. DC cells can trigger the activation of NK cells, in which the reverse signal transduction of IL-15R-IL-15 plays an important role. Great progression has been made in NK cell-based immunotherapy of tumor, in particular there are many new ways in NK cell innate recognition-based tumor biotherapy.