Department of Pathology and Comprehensive Cancer Center, The Ohio State University Columbus, OH, USA.
Am J Transl Res. 2013 Aug 15;5(5):470-80. eCollection 2013.
Cytotoxic T lymphocyte (CTL) response is a critical component of the immune response to tumors, therefore optimal induction of CTL responses to tumor antigens is highly desired for developing efficient cancer immunotherapy. IL-27 is a member of the IL-12 family of cytokines that is comprised of an IL-12 p40-related protein subunit, EBV-induced gene 3 (EBI3), and a p35-related subunit, p28. IL-27 functions through IL-27R and has been shown to have potent anti-tumor activity via activation of a variety of immune components, including anti-tumor CD8(+) T cell responses. However, the exact mechanisms of how IL-27 enhances anti-tumor CD8(+) T cell responses are not fully understood. In this paper we mainly discuss the evidences that suggest novel mechanisms by which IL-27 enhances anti-tumor CTL responses, including IL-27 inhibition of activation-induced cell death; the phenotypes of IL-27-stimulated CTLs; IL-27-induced CTL IL-10/IL-21 production and IL-27-mediated suppression of regulatory T cell responses. These evidences suggest that IL-27 may have a great potential to be utilized in boosting anti-tumor CTL responses in human cancer patients.
细胞毒性 T 淋巴细胞(CTL)应答是肿瘤免疫应答的关键组成部分,因此,为了开发有效的癌症免疫疗法,强烈需要诱导对肿瘤抗原的最佳 CTL 应答。IL-27 是细胞因子 IL-12 家族的一员,由 IL-12 p40 相关蛋白亚基、EB 病毒诱导基因 3(EBI3)和 p35 相关亚基 p28 组成。IL-27 通过 IL-27R 发挥作用,通过激活多种免疫成分,包括抗肿瘤 CD8+T 细胞反应,已显示出具有强大的抗肿瘤活性。然而,IL-27 增强抗肿瘤 CD8+T 细胞反应的确切机制尚未完全了解。在本文中,我们主要讨论了表明 IL-27 增强抗肿瘤 CTL 反应的新机制的证据,包括 IL-27 抑制激活诱导的细胞死亡;IL-27 刺激的 CTL 的表型;IL-27 诱导的 CTL IL-10/IL-21 产生和 IL-27 介导的调节性 T 细胞反应的抑制。这些证据表明,IL-27 可能具有很大的潜力,可用于增强人类癌症患者的抗肿瘤 CTL 反应。