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. Author manuscript; available in PMC: 2021 Jul 28.
Published in final edited form as: Trends Cancer. 2021 Jan 26;7(7):624–634. doi: 10.1016/j.trecan.2020.12.014

Figure 2. Stromal and Immune Signals Activate Stem Cell Signals and Enhance Therapeutic Resistance.

Figure 2.

The tumor microenvironment is composed of stromal cells such as cancer-associated fibroblasts (CAFs) and immune cell populations, including tumor-associated macrophages (TAMs), myeloid-derived suppressor cells (MDSCs), and T and B lymphocytes. These cells release signaling molecules that can activate stem cell programs within cancer cells. Both immune cells and fibroblasts can provide inflammatory cytokines (such as interleukin [IL]-6, IL-23, and IL-8) and growth factors (epidermal growth factor [EGF], insulin-like growth factor [IGF]-1, fibroblast growth factor [FGF]) that activate classical stem cell signals and drive resistance to both conventional and targeted therapies. Cancer stem cells can also resist immune-mediated killing by upregulating programmed death-ligand 1 (PD-L1) and CD80, perhaps making this aggressive subfraction an appealing target for immunotherapy.