新型免疫检查点——恶性肿瘤免疫治疗研究进展

New Immune Checkpoint: Advances in Immunotherapy for Malignant Tumors

针对程序性死亡受体1/程序性死亡配体1(PD-1/PD-L1)和细胞毒T淋巴细胞相关抗原4(CTLA-4)位点的免疫治疗药物已应用于临床,并且在临床中的地位和作用逐渐增强,然而这些药物获益人群有限,急需寻找新的治疗靶点并且探索出合适的免疫调节机制来提高恶性肿瘤治疗的疗效。本文从特异性免疫和非特异性免疫两方面对新型免疫检查点的起源、基础研究及相应靶点最新的临床研究结果和正在进行的临床研究进行综述,其中特异性免疫检查点包括T细胞免疫球蛋白黏蛋白3(TIM-3)、淋巴细胞活化基因3(LAG-3)、V区域Ig抑制子(VISTA)等,非特异性免疫检查点包括人类杀伤细胞免疫球蛋白样受体(KIR)、吲哚胺2,3-双加氧酶(IDO)、CD47,期望给临床及基础研究以提示。

The immunotherapeutic agents targeting programmed death-1/programmed cell death-ligand 1(PD-1/PD-L1)and cytotoxic T lymphocyte-associated antigen-4(CTLA-4)have been applied to clinical practice and are gaining increasing clinical significance.However,as limited population could benefit from these agents,it is imperative to identify new therapeutic targets and explore the appropriate immunoregulatory mechanisms to improve the therapeutic effects for malignant tumors.From the perspectives of specific immunity and non-specific immunity,this paper reviews the origin of the immune checkpoints,the basic studies,as well as the latest results of the completed and ongoing clinical studies,involving the specific immune checkpoints including T cell immunoglobulin mucin 3(TIM–3),lymphocyte activation gene-3(LAG-3),V-domain Ig suppressor of T-cell activation(VISTA),etc,and the non-specific immune checkpoints including killer cell immunoglobulin-like receptor(KIR),indoleamine 2,3-dioxygenase(IDO)and CD47,in an attempt to provide evidences for clinical and basic studies.