Myeloid cell collaboration network in the cancer-immunity cycle: origins, plasticity, and therapy

The transformative impact of immune checkpoint inhibitors highlights their limitations: the lack of response in cold tumors indicate the inherent deficiencies of T-cell-based monotherapies. In reality, the trajectory of anti-tumor immunity is shaped by a dynamic, collaborative network of myeloid cells within the tumor microenvironment. As the most abundant innate immune cells, myeloid cells do not operate in isolation; rather, they are part of a highly plastic and interconnected network that regulates every key step in the cancer-immunity cycle, such as antigen presentation, T-cell priming, tumor infiltration, and effector function. This article breaks new ground by mapping, for the first time, the complex architecture of the myeloid cell network: from its heterogeneous foundation based on developmental origins, to its dynamic plasticity influenced by microenvironmental signals, and to the intricate interplay of synergy and antagonism among subsets throughout different stages of the immune cycle. Ultimately, the core regulatory mechanisms governing this myeloid network are encapsulated in a tripartite model of spatiotemporal hubs–signal integration–functional output. This review, grounded in a network perspective, aims to shift cancer immunotherapy from a narrow focus on targeting individual nodes to a broader approach of modulating the entire ecosystem, providing a new strategy to overcome immunotherapy resistance.