CD4 and neoplasm: Advanced OS has highly heterogeneous histological patterns and is associated with an immunosuppressive microenvironment, which comprises cancer-associated fibroblasts, tumor-associated macrophages, vascular and perivascular cells, mesenchymal stem cells, dendritic cells, neutrophils, and CD4+ and CD8+ tumor-infiltrating lymphocytes, FoxP3+ T regs, B lymphocytes, and NK cells [12, 17••, 75–77].