Hence, therapeutic targeting of LTβR signaling, either by small molecule inhibitors of factors or activities identified here as crucial for LTβR signaling, e.g. LUBAC or the linear-ubiquitin-chain-forming activity of HOIP, or by using biotherapeutics that neutralize LTβR ligands or their interaction with LTβR, e.g. LTβR-Fc, could prove clinically useful to treat certain types of cancers, including HCC. This evidence concerns the gene RNF31 and cancer.