Diefenbach Andreas, Raulet David H
Department of Molecular and Cell Biology and Cancer Research Laboratory, University of California, Berkeley, CA 94720, USA.
Immunol Rev. 2002 Oct;188:9-21. doi: 10.1034/j.1600-065x.2002.18802.x.
Recent genetic studies have resurrected the concept that the adaptive and innate immune systems play roles in tumor surveillance. Natural killer (NK) cells recognize many tumor cells but not normal self cells, and they are thought to aid in the elimination of nascent tumors. Two main strategies are employed by NK cells to recognize tumor targets. Many tumor cells down-regulate class I major histocompatibility complex (MHC) molecules, thus releasing the NK cell from the inhibition provided by class I MHC-specific inhibitory receptors ('missing self recognition'). More recently, it has become clear that a stimulatory receptor expressed by NK cells, T cells and macrophages (NKG2D) recognizes ligands (MHC class I chain related [MIC], H6O, retinoic acid early inducible [Rae1] and UL16 binding proteins [ULBP]) that are up-regulated on tumor cells and virally infected cells but are not expressed well by normal cells. Ectopic expression of these ligands on tumor cells leads to the potent rejection of the tumors in vivo. Importantly, mice that previously rejected the ligand+ tumor cells develop T-cell immunity to the parental (ligand-) tumor cells. The recognition of induced-self ligands as a strategy to recognize abnormal self sets a precedent for a new immune recognition strategy of the innate immune system.
最近的遗传学研究重新提出了适应性免疫系统和先天性免疫系统在肿瘤监测中发挥作用的概念。自然杀伤（NK）细胞能够识别许多肿瘤细胞，但不识别正常的自身细胞，人们认为它们有助于消除新生肿瘤。NK细胞采用两种主要策略来识别肿瘤靶标。许多肿瘤细胞下调I类主要组织相容性复合体（MHC）分子，从而使NK细胞从I类MHC特异性抑制性受体提供的抑制中释放出来（“缺失自我识别”）。最近，越来越清楚的是，NK细胞、T细胞和巨噬细胞表达的一种刺激性受体（NKG2D）识别配体（MHC I类链相关分子[MIC]、H6O、视黄酸早期诱导分子[Rae1]和UL16结合蛋白[ULBP]），这些配体在肿瘤细胞和病毒感染细胞上上调，但在正常细胞中表达不佳。这些配体在肿瘤细胞上的异位表达导致体内肿瘤被有效排斥。重要的是，先前排斥配体阳性肿瘤细胞的小鼠会对亲本（配体阴性）肿瘤细胞产生T细胞免疫。将诱导性自身配体识别作为识别异常自身的一种策略，为先天性免疫系统的一种新的免疫识别策略开创了先例。
