Fig. 1: Interplay among DAMP proteins from dead cells, TLRs on immune cells, and cancer cells in the tumor microenvironment.
From: Interactions between tumor-derived proteins and Toll-like receptors
Anticancer drugs and irradiation induce apoptosis or necrosis in tumor cells. Several DAMP proteins (HMGB1, S100, HSP, API5, PAUF, RPS3, etc.) released from dying tumor cells stimulate immune cells or tumor cells after binding Toll-like receptors expressed on both of these cell types. Activated mature immune cells such as dendritic cells initiate adaptive immunity by educating tumor-specific T cells and secreting pro-inflammatory cytokines (TNF-α, IL-6, IL-12, IL-1β, IFN-β, etc.) that induce the secretion of DAMP proteins from tumor cells. TLR axis signaling in tumor cells induces the transcription of genes related to cell proliferation, chemotherapeutic resistance, invasion, and metastasis in tissues (e.g., lung tissue). In addition, tumors usually escape the immune response by altering the tumor microenvironment with immunosuppressive populations (Treg cells, MDSCs, M2 macrophages, etc.) and secretion of anti-inflammatory cytokines (IL-10, TGF-β, etc.).
