Finally, CXCR4 signaling, where TNC induces CXCL12 in tumor cells (through TLR4), but also binds to CXCL12 (again in the TN3–TN5 domains) thus trapping CD8T cells in the stroma, exerting a Janus function (i.e. both activation and inhibition) on yet another pathway (Murdamoothoo et al., 2021). Here, CXCL12 is linked to neoplasm.