Sun Chengpeng, Zhan Jianhao, Li Yao, Zhou Chulin, Huang Shuo, Zhu Xingen, Huang Kai
Department of Neurosurgery, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, P. R. China.
HuanKui Academy, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, China.
J Cell Mol Med. 2024 Apr;28(8):e18348. doi: 10.1111/jcmm.18348.
Tumour immune microenvironment (TIME) plays an indispensable role in tumour progression, and tumour-associated macrophages (TAMs) are the most abundant immune cells in TIME. Non-apoptotic regulated cell death (RCD) can avoid the influence of tumour apoptosis resistance on anti-tumour immune response. Specifically, autophagy, ferroptosis, pyroptosis and necroptosis mediate the crosstalk between TAMs and tumour cells in TIME, thus reprogram TIME and affect the progress of tumour. In addition, although some achievements have been made in immune checkpoint inhibitors (ICIs), there is still defect that ICIs are only effective for some people because non-apoptotic RCD can bypass the apoptosis resistance of tumour. As a result, ICIs combined with targeting non-apoptotic RCD may be a promising solution. In this paper, the basic molecular mechanism of non-apoptotic RCD, the way in which non-apoptotic RCD mediates crosstalk between TAMs and tumour cells to reprogram TIME, and the latest research progress in targeting non-apoptotic RCD and ICIs are reviewed.
肿瘤免疫微环境(TIME)在肿瘤进展中起着不可或缺的作用,而肿瘤相关巨噬细胞(TAM)是TIME中最丰富的免疫细胞。非凋亡性调节性细胞死亡(RCD)可避免肿瘤凋亡抗性对抗肿瘤免疫反应的影响。具体而言,自噬、铁死亡、焦亡和坏死性凋亡介导了TAM与TIME中肿瘤细胞之间的串扰,从而重塑TIME并影响肿瘤进展。此外,尽管免疫检查点抑制剂(ICI)已取得一些成果,但仍存在缺陷,即ICI仅对某些人有效,因为非凋亡性RCD可绕过肿瘤的凋亡抗性。因此,ICI联合靶向非凋亡性RCD可能是一种有前景的解决方案。本文综述了非凋亡性RCD的基本分子机制、非凋亡性RCD介导TAM与肿瘤细胞之间串扰以重塑TIME的方式,以及靶向非凋亡性RCD和ICI的最新研究进展。