Cellular Immunology Unit, Division of Immunology, Transplantation and Infectious Diseases, Istituto Scientifico San Raffaele, Milan, Italy.
PLoS One. 2010 Jan 13;5(1):e8646. doi: 10.1371/journal.pone.0008646.
CD1d-restricted invariant NKT (iNKT) cells are a subset of T lymphocytes endowed with innate effector functions that aid in the establishment of adaptive T and B cell immune responses. iNKT cells have been shown to play a spontaneous protective role against experimental tumors. Yet, the interplay between iNKT and tumor-specific T cells in cancer immune surveillance/editing has never been addressed. The transgenic adenocarcinoma of the mouse prostate (TRAMP) is a realistic model of spontaneous oncogenesis, in which the tumor-specific cytotoxic T cell (CTL) response undergoes full tolerance upon disease progression.
We report here that lack of iNKT cells in TRAMP mice resulted in the appearance of more precocious and aggressive tumors that significantly reduced animal survival. TRAMP mice bearing or lacking iNKT cells responded similarly to a tumor-specific vaccination and developed tolerance to a tumor-associated antigen at comparable rate.
Hence, our data argue for a critical role of iNKT cells in the immune surveillance of carcinoma that is independent of tumor-specific CTL.
CD1d 限制性不变自然杀伤 T(iNKT)细胞是一群具有先天效应功能的 T 淋巴细胞亚群，有助于建立适应性 T 和 B 细胞免疫反应。iNKT 细胞已被证明在实验性肿瘤中发挥自发的保护作用。然而，iNKT 细胞与肿瘤特异性 T 细胞在癌症免疫监视/编辑中的相互作用尚未得到解决。小鼠前列腺腺癌（TRAMP）是自发发生肿瘤的现实模型，其中肿瘤特异性细胞毒性 T 细胞（CTL）反应在疾病进展时会完全耐受。
我们在这里报告，TRAMP 小鼠中缺乏 iNKT 细胞会导致更早熟和侵袭性肿瘤的出现，这显著降低了动物的存活率。携带或缺乏 iNKT 细胞的 TRAMP 小鼠对肿瘤特异性疫苗有类似的反应，并以相似的速度对肿瘤相关抗原产生耐受。
因此，我们的数据表明，iNKT 细胞在对癌的免疫监视中起着关键作用，而与肿瘤特异性 CTL 无关。
