Department of Medicine, Division of Hematology/Oncology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
Clin Immunol. 2011 Aug;140(2):184-95. doi: 10.1016/j.clim.2011.04.017. Epub 2011 May 13.
Invariant natural killer T-cells ('iNKT') are the best-known CD1d-restricted T-cells, with recently-defined roles in controlling adaptive immunity. CD1d-restricted T-cells can rapidly produce large amounts of Th1 and/or Th2//Treg/Th17-type cytokines, thereby regulating immunity. iNKT can stimulate potent anti-tumor immune responses via production of Th1 cytokines, direct cytotoxicity, and activation of effectors. However, Th2//Treg-type iNKT can inhibit anti-tumor activity. Furthermore, iNKT are decreased and/or reversibly functionally impaired in many advanced cancers. In some cases, CD1d-restricted T-cell cancer defects can be traced to CD1d(+) tumor interactions, since hematopoietic, prostate, and some other tumors can express CD1d. Ligand and IL-12 can reverse iNKT defects and therapeutic opportunities exist in correcting such defects alone and in combination. Early stage clinical trials have shown potential for reconstitution of iNKT IFN-gamma responses and evidence of activity in a subset of patients, with rational new approaches to capitalize on this progress ongoing, as will be discussed here.
不变自然杀伤 T 细胞（“iNKT”）是最著名的 CD1d 限制性 T 细胞，其在控制适应性免疫方面的作用最近得到了定义。CD1d 限制性 T 细胞可以迅速产生大量 Th1 和/或 Th2//Treg/Th17 型细胞因子，从而调节免疫。iNKT 通过产生 Th1 细胞因子、直接细胞毒性和激活效应物来刺激有效的抗肿瘤免疫反应。然而，Th2//Treg 型 iNKT 可以抑制抗肿瘤活性。此外，许多晚期癌症中 iNKT 减少和/或可逆性功能受损。在某些情况下，可以追踪到 CD1d(+)肿瘤相互作用导致 CD1d 限制性 T 细胞的癌症缺陷，因为造血细胞、前列腺和一些其他肿瘤可以表达 CD1d。配体和 IL-12 可以逆转 iNKT 缺陷，并且存在单独和联合纠正这种缺陷的治疗机会。早期临床试验表明，iNKT IFN-γ 反应的重建具有潜力，并且在一部分患者中具有活性的证据，正在进行利用这一进展的合理新方法，本文将对此进行讨论。
