A comprehensive review of phytochemicals targeting macrophages for the regulation of colorectal cancer progression

Phytochemicals are natural compounds derived from plants, and are now at the forefront of anti-cancer research. Macrophage immunotherapy plays a crucial role in the treatment of colorectal cancer (CRC). In the context of colorectal cancer, which remains highly prevalent and difficult to treat, it is of research value to explore the potential mechanisms and efficacy of phytochemicals targeting macrophages for CRC treatment. The aim of this study was to gain insight into the role of phytochemical-macrophage interactions in regulating CRC and to provide a theoretical basis for the development of new therapeutic strategies in the future. This review discusses the potential immune mechanisms of phytochemicals for the treatment of CRC by summarizing research of phytochemicals targeting macrophages. We reviewed the PubMed, EMBASE, Web of Science and CNKI databases from their initial establishment to July 2023 to classify and summaries phytochemicals according to their mechanism of action in targeting macrophages. The results of the literature review suggest that phytochemicals interfere with CRC development by affecting macrophages through four main mechanisms. Firstly, they modulate the production of cytotoxic substances, such as NO and ROS, by macrophages to exert anticancer effects. Secondly, phytochemicals polarize macrophages towards the M1 phenotype, inhibit M2 polarisation and enhance the anti-tumour immune responses. Thirdly, they enhance the secretion of macrophage-derived cytokines and alter the tumour microenvironment, thereby inhibiting tumor growth. Finally, they activate the immune response by targeting macrophages, triggering the recruitment of other immune cells, thereby enhancing the immune killing effect and exerting anti-tumor effects. These findings highlight phytochemicals as potential therapeutic strategies to intervene in colorectal cancer development by modulating macrophage activity, providing a strong theoretical basis for future clinical applications. Phytochemicals exhibit potential anti-tumour effects by modulating macrophage activity and intervening in the colorectal cancer microenvironment by multiple mechanisms.