机体免疫应答的动态变化及空间差异是疾病精细化治疗的理论基础之一，同一免疫调节分子在不同时空条件下的功能可能截然不同。T细胞免疫球蛋白黏蛋白分子-3（T cell immunoglobulin and mucin-containing protein-3，TIM-3）是新近鉴定出的免疫检查点分子，与CTLA-4、PD-1 等一样参与了免疫细胞稳态调控，TIM-3 的异常高表达与肿瘤、慢性病毒感染的相关性使其成为免疫靶向治疗的关注点。靶向免疫检查点分子的临床治疗给患者带来了希望，但也存在效率不高、耐药乃至副作用明显等情况，问题的解决有赖于该类分子精细调控机制的阐明。大多数数据显示TIM-3 具免疫抑制作用，但也有相反的报道。TIM-3 的配体多样，胞内信号转导机制仍不十分明确。此外，血清中存在的可溶性TIM-3 蛋白的功能及临床意义目前尚不清楚。如果免疫系统进化的过程中也赋予了TIM-3 多重的免疫调节功能，阐明其调控机制必将对后续的应用研究提供重要参考。

Dynamic change and spatial characteristics of immune response is one of the fundamental theories of precision medical treatment. One certain immune regulator may have totally different functions under different temporal and spatial distribution. T cell immunoglobulin domain and mucin domain protein-3 (TIM-3) is a recently identified immune checkpoint inhibitor. Like PD-1 and CTLA-4, TIM-3 contributes to immune homeostasis. Recently, TIM-3 has attracted much attention as its dysregulated over-expression was approved to be associated with tumors and chronic viral infections.Strategies targeting immune checkpoints are now showing therapeutic prospect. However, the low efficiency rate, therapy resistance and even side effects still exist, which call for precise mechanisms investigation. Most of the research indicates the immune inhibitory effect of TIM-3; still, there are some reports on opposite conclusion. TIM-3 has multiple ligands,and the intra-cellular signaling mechanism is still unclear. In addition, the function and clinical significance of soluble TIM-3 protein in plasma remain unclear. If TIM-3 acquired multiple functions following the evolution of immune system,clarify the mechanisms by which TIM-3 regulates immune response will provided much important information for its further investigation.

国家重点基础研究发展计划（973 计划）资助项目（No.2013CB530506）;国家自然科学基金资助项目（No. 81471540）;北京市自然科学基金重点项目资助（No. 7141007）