Regulation of Cancer Stem Cells in the Tumor Microenvironment

Cancer stem cells (CSCs) represent a subpopulation of cancer cells characterized by their capacity for self-renewal, differentiation, and tumorigenicity. CSCs exist along a spectrum of stemness regulated by both intrinsic factors and extrinsic signals from the tumor microenvironment (TME). The TME is composed of diverse cell types such as stromal and immune cells, and also physical factors such as the extracellular matrix and hypoxia. Environmental signals originating from the TME can induce non-CSCs to acquire stem-like traits, while CSCs in turn modulate the TME by recruiting and reprogramming immune and stromal cells. Analogous to normal stem cell niches, CSCs reside in or construct supportive niches that promote stemness, metastasis, immune evasion, and therapy resistance. This reciprocal interaction between CSCs and the TME underscores the complexity of cancer stemness and presents challenges and opportunities for therapeutics.