Here, several pathways could be involved as we saw that TNC promoted conversion of macrophages into a pro-tumoral M2 phenotype involving Toll Like Receptor 4 (TLR4) and activated C-X-C chemokine receptor type 4 (CXCR4) signaling causing immobilization of CD8+ T cells in the stroma thereby inhibiting anti-tumor immunity (17, 45, 49). Here, TLR4 is linked to neoplasm.