Research Centre, Centre Hospitalier de l'Université de Montréal-Hôpital Notre-Dame, Université de Montréal and Institut du Cancer de Montréal, Montreal, Quebec, Canada.
J Immunol. 2009 Dec 15;183(12):7752-60. doi: 10.4049/jimmunol.0901004.
Previous cancer vaccination approaches have shown some efficiency in generating measurable immune responses, but they have rarely led to tumor regression. It is therefore possible that tumors emerge with the capacity to down-regulate immune counterparts, through the local production of immunosuppressive molecules, such as IDO. Although it is known that IDO exerts suppressive effects on T cell functions, the mechanisms of IDO regulation in tumor cells remain to be characterized. Here, we demonstrate that activated T cells can induce functional IDO expression in breast and kidney tumor cell lines, and that this is partly attributable to IFN-gamma. Moreover, we found that IL-13, a Th2 cytokine, has a negative modulatory effect on IDO expression. Furthermore, we report IDO expression in the majority of breast and kidney carcinoma samples, with infiltration of activated Th1-polarized T cells in human tumors. These findings demonstrate complex control of immune activity within tumors. Future immune therapeutic interventions should thus include strategies to counteract these negative mechanisms.
先前的癌症疫苗接种方法在产生可测量的免疫反应方面显示出了一定的效果，但它们很少能导致肿瘤消退。因此，肿瘤可能会通过局部产生免疫抑制分子（如 IDO）来下调免疫对应物，从而出现。虽然已知 IDO 对 T 细胞功能具有抑制作用，但 IDO 在肿瘤细胞中的调节机制仍有待阐明。在这里，我们证明激活的 T 细胞可以在乳腺和肾肿瘤细胞系中诱导功能性 IDO 表达，这部分归因于 IFN-γ。此外，我们发现 Th2 细胞因子 IL-13 对 IDO 表达具有负调节作用。此外，我们报告了在大多数乳腺癌和肾癌样本中存在 IDO 表达，并在人类肿瘤中浸润了激活的 Th1 极化 T 细胞。这些发现证明了肿瘤内免疫活性的复杂控制。因此，未来的免疫治疗干预措施应包括对抗这些负性机制的策略。
