Figure 2.

A schematic of the proposed temporo-spatial organization of the TME. Cells must first undergo neoplastic transformation, allowing for the creation of a permissive micro-ecological niche. Neighboring cells, including adipocytes, fibroblasts, and macrophages, among others, can adopt a cancer-associated phenotype, with complex, pro-tumorigenic effects. Hypoxia induced by cell proliferation and metabolic changes encourage lymph and blood vessel invasion, increasing infiltration by inflammatory cells. Furthermore, angiogenesis and lymphangiogenesis create increased opportunity for neoplastic cell spread and metastasis (created with Biorender.com).