Fig. 8: MYC activation in neoplastic cells reprograms the prostate TME.
From: Convergent alterations in the tumor microenvironment of MYC-driven human and murine prostate cancer
A MYC activation in luminal epithelial cells leads to the induction of benign Ly6d/Krt6a-expressing epithelial population (Reactive Epithelial cells) in the basal compartment of prostate glands. B At the precursor stage, the TME is pro-inflammatory, with upregulated interferon signaling in both MYC-expressing luminal cells and Reactive Basal cells, and (C) enrichment of various immune cells in the TME, including mast cells, T cells, and Trem2-expressing macrophages. D As MYC-expressing luminal cells progress to invasive carcinoma, there is a pro-inflammatory to immunosuppressive switch with downregulation of inflammatory response pathways and IL6 JAK STAT3 signaling, and enrichment of immunosuppressive cell types, including regulatory T cells (Tregs), myeloid-derived suppressive cells (MDSCs), and Trem2-expressing macrophages. E Secretion of TGFB by Trem2-expressing macrophages activates TGFB signaling and EGR4 transcription factor activity in fibroblasts, resulting in a desmoplastic CAF population expressing Timp1 and reactive-stroma-associated ECM proteins such as collagen. Graphical abstract created in Biorender.com. Figure 8 created with BioRender.com released under a Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International license.
