Monocytes (Mos) are immune cells that critically regulate cancer, enabling tumor growth and modulating metastasis. Mos can give rise to tumor-associated macrophages (TAMs) and Mo-derived dendritic cells (moDCs), all of which shape the tumor microenvironment (TME). Thus, understanding their roles in the TME is key for improved immunotherapy. Concurrently, various biological and mechanical factors including changes in local cytokines, extracellular matrix production, and metabolic changes in the TME affect the roles of monocytic cells. As such, relevant TME models are critical to achieve meaningful insight on the precise functions, mechanisms, and effects of monocytic cells. Notably, murine models have yielded significant insight into human Mo biology. However, many of these results have yet to be confirmed in humans, reinforcing the need for improved in vitro human TME models for the development of cancer interventions. Thus, this chapter (1) summarizes current insight on the tumor biology of Mos, TAMs, and moDCs, (2) highlights key therapeutic applications relevant to these cells, and (3) discusses various TME models to study their TME-related activity. We conclude with a perspective on the future research trajectory of this topic.
Keywords: 2D versus 3D; Autologous cell therapy; Cancer; Combinational immunotherapy; Differentiation and commitment; Heterogeneity; Human versus mouse; Macrophages; Microfluidic models; Monocyte-derived dendritic cells; Monocytes; Ontogeny; Organ-on-a-chip; Personalized precision medicine; Tumor microenvironment.