Given that 4-1BB signaling is currently employed to treat cancers in the clinic in the forms of agonistic anti-4-1BB or chimeric antigen receptors containing the 4-1BB cytoplasmic domain to enhance anti-tumor CD8+ T cell responses [5], [40], the cross-talk between the Wnt and NF-κB signaling pathways upon 4-1BB stimulation needs to be fully elucidated to understand the therapeutic mechanisms of 4-1BB. This evidence concerns the gene CD8A and cancer.