Potential therapeutic targets in myeloid cell therapy for overcoming chemoresistance and immune suppression in gastrointestinal tumors
Jiawei Fan, Jianshu Zhu, He Zhu, Hong Xu
Abstract
In the tumor microenvironment (TME), myeloid cells play a pivotal role. Myeloid-derived immunosuppressive cells, including tumor-associated macrophages (TAMs) and myeloid-derived suppressor cells (MDSCs), are central components in shaping the immunosuppressive milieu of the tumor. Within the TME, a majority of TAMs assume an M2 phenotype, characterized by their pro-tumoral activity. These cells promote tumor cell growth, angiogenesis, invasion, and migration. In contrast, M1 macrophages, under appropriate activation conditions, exhibit cytotoxic capabilities against cancer cells. However, an excessive M1 response may lead to pro-tumoral inflammation. As a result, myeloid cells have emerged as crucial targets in cancer therapy. This review concentrates on gastrointestinal tumors, detailing methods for targeting macrophages to enhance tumor radiotherapy and immunotherapy sensitivity. We specifically delve into monocytes and tumor-associated macrophages' various functions, establishing an immunosuppressive microenvironment, promoting tumorigenic inflammation, and fostering neovascularization and stromal remodeling. Additionally, we examine combination therapeutic strategies. • Myeloid cells have a dual impact on the gastrointestinal tumor microenvironment. • Monocytes and macrophages contribute to tumor stem cell maintenance and the creation of an immunosuppressive environment. • MDSCs suppress key immune cells, aiding in targeting tumor resistance. • Targeted strategies, combined with radiotherapy and immunotherapy, enhance gastrointestinal cancer treatment efficacy.