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靶向SHP1和SHP2以抑制肿瘤并增强免疫监视。

Targeting SHP1 and SHP2 to suppress tumors and enhance immunosurveillance.

作者信息

Zhao Yijun, Jiang Linjia

机构信息

Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong 510000, China.

Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong 510000, China.

出版信息

Trends Cell Biol. 2025 Aug;35(8):667-677. doi: 10.1016/j.tcb.2024.10.008. Epub 2024 Nov 21.

Abstract

The nonreceptor tyrosine phosphatases (PTPS) SHP1 and SHP2 have crucial roles in dephosphorylating an array of substrates involved in pathways comprising receptor tyrosine kinases (RTKs) and immune receptors. This regulation maintains a delicate balance between the activation and inhibition of signal transduction, ensuring appropriate biological outcomes. In this review, we summarize research focused on elucidating the functions of SHP1 and SHP2 in hematopoiesis, immune regulation, and tumor biology, emphasizing recent findings related to cancer-driven immune evasion. Furthermore, we highlight the significant effects of SHP1 and SHP2 inhibitors in enhancing cancer treatment, specifically through the facilitation of chemotherapy and augmentation of immune activation.

摘要

非受体酪氨酸磷酸酶(PTPS)SHP1和SHP2在使一系列参与包括受体酪氨酸激酶(RTK)和免疫受体的信号通路的底物去磷酸化过程中发挥关键作用。这种调节维持了信号转导激活与抑制之间的微妙平衡,确保了适当的生物学结果。在本综述中,我们总结了旨在阐明SHP1和SHP2在造血、免疫调节和肿瘤生物学中的功能的研究,重点关注与癌症驱动的免疫逃逸相关的最新发现。此外,我们强调了SHP1和SHP2抑制剂在增强癌症治疗方面的显著作用,特别是通过促进化疗和增强免疫激活来实现。

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