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The TME is a complex and multi-layered structure, primarily consisting of cancer cells, cancer-associated fibroblasts (CAFs), cells that suppress the immune system (such as tumor-associated macrophages [TAMs], myeloid-derived suppressor cells [MDSCs], and regulatory T cells), cells that activate the immune system (including natural killer [NK] cells, dendritic cells [DCs], and T cells), and a variety of signaling molecules [33,34,35,36]

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Following from previous work that sought to identify sequence determinants of S fibrillation, a library-based -lactamase tripartite fusion construct in which S was inserted between Blac fragments and probed for aggregation, identified mutations within the P1/P2 regions that impacted on the ability of S to aggregate