“T cell exhaustion” at the tumor site constitutes thus the third stumbling block, in addition to the poor naïve repertoire of self antigen-specific CD8 T cells (low affinity and precursor frequency: first stumbling block) and the poor priming capacity against tumors (inefficient tumor antigen presentation and co-stimulation by tumors: second stumbling block) [reviewed in Ref. This evidence concerns the gene CD8A and neoplasm.