英文原题:Protein tyrosine kinases in dendritic cell-mediated anti-cancer immunity.
Protein tyrosine kinases in dendritic cell-mediated anti-cancer immunity.
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树突状细胞(DC)是最有效的抗原呈递细胞,连接固有免疫与适应性免疫,对肿瘤免疫监视至关重要。其功能受蛋白酪氨酸激酶(PTK)精确调控,PTK整合外部刺激和内部细胞应激信号,控制DC的成熟、迁移和抗原呈递。本综述系统整合了关于PTK在DC介导的抗肿瘤免疫中作用的现有知识,重点分析其在不同人类和小鼠DC亚群中的差异表达和功能——包括经典DC(cDC1、cDC2)、浆细胞样DC(pDC)和单核细胞来源DC。我们重点阐述特定PTK家族(如TAM、PDGFR、SRC、JAK)如何将病原体和损伤相关信号转化为定制化免疫应答。此外,我们讨论临床已批准的PTK抑制剂对DC功能的双重影响,其可根据情境增强或抑制抗肿瘤免疫。最后,我们评估将PTK靶向药物与DC疫苗或免疫检查点阻断相结合的转化策略,为利用PTK-DC串扰开发更有效的联合免疫治疗提供依据。
Dendritic cells (DCs), the most proficient antigen-presenting cells, bridge innate and adaptive immunity and are critical for anti-cancer immune surveillance. Their function is precisely regulated by protein tyrosine kinases (PTKs), which integrate signals from external stimuli and internal cellular stress to control DC maturation, migration, and antigen presentation.
This review systematically synthesizes current knowledge on PTK roles in DC-mediated anti-tumor immunity, with a focused analysis of their differential expression and function across human and mouse DC subsets-including conventional (cDC1, cDC2), plasmacytoid (pDC), and monocyte-derived DCs.
We highlight how specific PTK families (e. g. , TAM, PDGFR, SRC, JAK) translate pathogen- and damage-associated signals into tailored immune responses.
Furthermore, we discuss the dual impact of clinically approved PTK inhibitors on DC function, which can either enhance or suppress anti-tumor immunity depending on context.
Finally, we evaluate translational strategies that combine PTK-targeted agents with DC-based vaccines or immune checkpoint blockade, offering a rationale for exploiting PTK-DC crosstalk to develop more effective combinatorial immunotherapies.
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