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1350~1355.T细胞免疫球蛋白黏蛋白分子-3 在肿瘤免疫中的作用和机制[J].姜霁峰,陶荣.中国肿瘤生物治疗杂志,2017,24(12)
T细胞免疫球蛋白黏蛋白分子-3 在肿瘤免疫中的作用和机制    点此下载全文    点此浏览HTML全文
姜霁峰  陶荣
上海交通大学医学院附属新华医院血液内科,上海200092,上海交通大学医学院附属新华医院血液内科,上海200092
基金项目:上海市教育委员会高峰高原学科建设资助项目(No.20152219)
DOI:10.3872/j.issn.1007-385X.2017.12.002
摘要:
      应用单克隆抗体阻断PD-1、CTLA-4 等免疫检查点已在肿瘤免疫治疗中取得了一定成效,但尚有部分患者对免疫检查点阻断剂疗效不佳,其机制可能为存在其他抑制性旁路。T细胞免疫球蛋白黏蛋白分子-3(T cell immunolobulin and mucin-containing protein-3,TIM-3)是一种可表达于多种免疫细胞,并具有重要调控作用的免疫检查点分子。已有研究报道多种肿瘤外周血和肿瘤浸润性T细胞中存在TIM-3 高表达,并与预后不良相关。抗肿瘤免疫中,高表达TIM-3 的T细胞、DC及单核巨噬细胞,可抑制肿瘤免疫应答。临床前研究显示,抗TIM-3 单抗联合抗PD-1 单抗可发挥协同抗肿瘤效应。TIM-3 单克隆抗体已进入临床试验阶段。然而,TIM-3 在调控免疫细胞中的部分功能尚待阐明,进一步理解TIM-3 的免疫调节机制有助于推动基于阻断TIM-3 抗肿瘤免疫治疗的临床应用。
关键词:肿瘤免疫  免疫检查点;T细胞免疫球蛋白黏蛋白分子-3
Current understanding of the role of T cell immunoglobulin and mucin-containing protein-3 in cancer immunity    Download Fulltext
JIANG Jifeng  TAO Rong
Department of Hematology Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine,Shanghai 200092, China and Department of Hematology Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine,Shanghai 200092, China
Fund Project:Project supported by Shanghai Municipal Education Commission-Gaofeng Clinical Medicine Grant (No. 201522119)
Abstract:
      The application of monoclonal antibodies to block immune checkpoints including PD-1, CTLA-4 has demonstrated a good efficacy in cancer immunotherapy. However, some patients poorly responded to these immune checkpoints blockers. One probable mechanism for this failure in igniting the antitumor effect was that other inhibitory molecules over expressed in these cases. As an immune checkpoint, T cell immunolobulin and mucin-containing protein-3(TIM-3) is widely expressed in a variety of immune cells, and palys an important role in the regulation of immune response. Many studies showed that lymphocytes from patient peripheral blood or tumor-infiltrating lymphocytes expressed high levels of TIM-3, which was associated with poor outcome. T cell, DC cell and mononuclear phagocytes with over-expressed TIM-3 showed significant inhibitory effects on antitumor immune response. In preclinical studies, combined blockade of TIM-3 and PD-1 with antibodies showed a synergistic effect on antitumor immunity. Clinical trials are underway to evaluate the safety and efficacy of TIM-3 monoclonal antibodies in cancer patients. However, the regulatory role of TIM-3 on immune cells has not been fully clarified, better understanding of the immune modulatory mechanism of TIM-3 helps to develop effective treatment strategy of blockade of TIM-3 in future clinical trials.
Keywords:cancer immunity  immune checkpoint  T cell immunoglobulin and mucin-containing protein-3
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