One of the most representative lncRNAs was HOTTIP, and it caused various changes according to its origin: the M1 macrophage-derived exosomal lncRNA HOTTIP proved to strongly suppressed tumor progression via the upregulation of the TLR5/NF-κB pathway [143]; however, when it was secreted by cancer stem cells in OSCC, it then promoted M2 macrophage polarization, inhibited CD4+ T-cell proliferation and IFN-γ production, and facilitated tumor progression and immunosuppression via the LAMC2-mediated PI3K/AKT pathway [144]. This evidence concerns the gene CD4 and neoplasm.