Tumor-derived exosomes also polarize the macrophages in the TME to form tumor-associated macrophages (TAMs) that can bi-directionally modulate the TME into an anti-inflammatory, immunosuppressed state by releasing exosomes carrying miRNAs such as miR-21 and miR-223, thereby leading to enhanced drug resistance, suppression of cancer cell apoptosis and activation of the PI3K/AKT signaling pathway [93]. The gene discussed is PIK3CA; the disease is neoplasm.