The two major strategies to generate tumor-specific T cells involve either altering the antigen-binding sites of the T-cell receptor (TCR) which require major histocompatibility complex (MHC)-dependent antigen presentation, or engineering a novel recombinant receptor, the chimeric antigen receptor (CAR), that activates T cells in an MHC-unrestricted manner, bypassing the downregulation of MHC complexes caused by glioma cells both on tumor and antigen-presenting cells [111]. This evidence concerns the gene HLA-C and glioma.