自然杀伤(NK)细胞是固有免疫系统中发挥细胞毒性作用的淋巴细胞,而NKG2D是NK细胞最重要的活化性受体之一,它通过识别靶细胞表面的配体NKG2DL来传递活化信号并激活免疫细胞对靶细胞发挥杀伤作用,在肿瘤免疫治疗中发挥重要作用.肿瘤微环境(TME)内存在多种机制调节NKG2D和NKG2DL的表达,从而影响免疫系统对肿瘤细胞的清除并导致肿瘤逃逸.NKG2D的强激活作用及其配体NKG2DL在肿瘤细胞上的选择性表达,使NKG2D/NKG2DL轴成为肿瘤免疫治疗的潜在靶点.本文围绕NKG2D/NKG2DL轴介导的免疫监视与逃逸的双重作用,揭示重塑TME对肿瘤免疫的重要性;并就干预NKG2D/NKG2DL轴在肿瘤免疫治疗中的研究进展进行综述,为基于NKG2D/NKG2DL开发免疫治疗药物提供可靠依据和新思路.

The Wnt/β-catenin signaling pathway has been one of the most common molecular targets of cancer treatment, owing to its involvement in the formation and development of many malignant tumors. It is also significantly involved in tumor immunoregulation, and abnormally activated Wnt/β-catenin signaling is closely linked to the immunosuppressive microenvironment of tumors. Immune checkpoint inhibitors have been widely studied and used for cancer treatment, but using inhibitors targeting programmed cell death protein 1（PD-1）/programmed cell death ligand 1（PD-L1） and cytotoxic T lymphocyte antigen-4（CTLA-4） results in tumor drug resistance and low patient response rates. Activation of the Wnt/β-catenin pathway inhibits CD8+T cell infiltration into the tumor microenvironment, which inhibits anti-tumor immune response and induces immune checkpoint inhibitor resistance. This review focuses on the relationship between the Wnt/β-catenin signaling pathway and immune checkpoints and reviews the research progress on the treatment of malignant tumors utilizing a combination of Wnt/β-catenin and immune checkpoint inhibitors.