Remarkably, recent reports in murine transplantable and carcinogen-induced tumor models support the operational dominance of TNFR- over LTβR-mediated signaling for HEV/TLS neogenesis in the TME (40, 44), findings which contrast with the canonical importance of LTβR-mediated signaling for HEV/TLS formation in normal tissues and in ontogenic secondary lymphoid organogenesis (1, 29, 30, 40, 44). This evidence concerns the gene LTBR and neoplasm.