The Role of Cancer Stem Cell-Derived Exosomes in Cancer Progression

Figure 4

CSC-Exos regulate cancer cells to evade immune surveillance. MiRNAs contained in nasopharyngeal carcinoma (NPC) cell-derived exosomes downregulate the MAPKI and JAK/STAT pathways to impair T-cell proliferation, differentiation, and cytokine secretion. miRNA-21 and miRNA-29a can bind to Toll-like receptor 8 (TLR8) on the surface of tumor-associated macrophages through the action of CSC-Exos, triggering the NF-κB pathway and the secretion of interleukin-6 (IL-6) to induce evasion of immune surveillance. Exosomes derived from pancreatic cancer (PaCa) cells contain miR-212-3p, which inhibits the expression of regulatory factor X-associated protein (RFXAP), resulting in a decrease in the expression of MHC II molecules (molecules on the surface of B cells) and induction of immune tolerance. Breast cancer-derived exosomes inhibit the proliferation of T cells through TGF-β1, interfering with normal immune system function. The lncRNA KCNQ1OT1 loaded in colorectal cancer cell-derived exosomes (CRC-Exos) mediates the miR-30a-5p/USP22 pathway to regulate the ubiquitination of PD-L1 and inhibits the CD8+ T-cell response, thereby promoting colorectal cancer cell evasion of immune surveillance. Macrophage immunomodulation by breast cancer cell-derived exosomes requires Toll-like receptor 2-mediated activation of the NF-κB pathway, which induces pro-inflammatory activity of distant macrophages in cancer progression.