Pathophysiological roles of monocytes and macrophages in cancer.

Monocytes and macrophages are versatile immune sentinels that are present in nearly all tissues, where they continually adapt to local cues. In cancer, their functions are context-dependent - often linked to tumour growth and poor prognosis but also capable of driving potent antitumour immunity. To explain this dichotomy, we frame cancer cells as 'infectious self', having both pathogen-like and self-like features. In turn, monocytes and macrophages adopt modular programmes across primary and metastatic tumour sites - as well as along haematogenous, lymphatic and transcoelomic routes of dissemination - that are shaped by oncogenic lesions, cancer cell differentiation states, tissue perturbations and organism-level variables. These cells are promising yet challenging therapeutic targets. Opportunities include blocking the recruitment, differentiation and scavenging activity of pro-tumour monocytes and macrophages; activating pattern recognition receptor signalling pathways and lymphocyte help; inducing cancer cell phagocytosis; and rewiring key intracellular signalling nodes. Emerging cellular and gene-based approaches - such as chimeric receptor engineering and in vivo target delivery - further expand this toolkit and underscore the potential to reprogramme monocyte and macrophage responses for durable control of solid tumours.