CAR modification confers T cells with “de novo” defined antigen specificities independently of both the natural TCR and major histocompatibility complex (MHC) restriction, which not only overcomes the downregulation of Human Leucocyte Antigen (HLA, human MHC) molecules frequently observed in cancer cells, but also widens the repertoire of actionable targets due to scFv-mediated antigen recognition of non-protein epitopes, thus greatly expanding the potentials of ACT for cancer immunotherapy (1, 3, 4). This evidence concerns the gene HLA-C and cancer.