摘要
以靶向PD-1/PD-L1和CTLA-4为代表的免疫检查点阻断治疗在实体瘤的治疗中取得了不俗疗效,但仅有不到30%的患者能够从中受益的现实表明,还存在其他免疫检查点分子介导的免疫抑制。B7H3属于免疫球蛋白超家族B7家族成员,与CTLA-4/PD-1主要表达在T细胞并介导后者的免疫抑制或耗竭不同,B7H3蛋白不仅诱导性表达在免疫细胞,还组成性高表达在多种肿瘤细胞和肿瘤相关脉管系统。B7H3不仅能够激活多条信号通路直接促进肿瘤细胞恶性表型,还可以通过重塑肿瘤免疫抑制微环境间接促进肿瘤的进展、转移和耐药。因此,基于B7H3的多项靶向抗肿瘤策略,包括特异性抗体、抗体偶联药物及CAR-T细胞等均已进入临床试验并展示出较好的应用前景。但总体而言,该领域的研究依然处于探索阶段,在相互作用受体的鉴定、降低毒性、打破耐药及联合用药策略优化等方面还面临着许多问题和挑战亟待突破。
Immune checkpoint blockade(ICB)therapy,represented by PD-1/PD-L1 and CTLA-4,has achieved remarkable efficacy in the treatment of solid tumors;However,only less than 30%of the patients benefit from it,suggesting that there still exists other immune checkpoints molecule-mediated immunosuppression.B7H3 is a member of the B7 immunoglobulin superfamily.Unlike CTLA-4 or PD-1 which is mainly expressed in T cells to mediate their immunosuppression or depletion,B7H3 is not only inducibly expressed in immune cells,but also constitutively highly expressed in various tumor cells and tumor-associated vascular systems.B7H3 not only directly promotes the malignant biological phenotypes of tumor cells by activating multiple signaling pathways,but also indirectly promotes tumor progression,metastasis and drug resistance by remodeling tumor immunosuppressive microenvironment.Therefore,several targeted anti-tumor strategies targeting B7H3,including specific antibodies,antibody-drug conjugation(ADC)and CAR-T,have entered clinical trials and shown promising application prospects.However,in general,the research of B7H3 is still in the exploratory stage.There are still many bottlenecks and challenges to be overcome in the identification of reciprocal receptors,reduction of toxicity,breaking drug resistance,and optimization of combination drug therapy,etc.
作者
黄明燕
刘秋燕
HUANG Mingyan;LIU Qiuyan(National Key Laboratory of Immunity&Inflammation,Institute of Immunology,Naval Medical University,Shanghai 200433,China)
出处
《中国肿瘤生物治疗杂志》
CAS
CSCD
北大核心
2023年第5期365-372,共8页
Chinese Journal of Cancer Biotherapy
基金
国家自然科学基金(No.31770966)。
