In line with this defective anti-tumor immune response caused by exhausted cytotoxic TILs by the engagement of the CD94/NKG2A-HLA-E/β2m axis, we confirmed in this study, based on an independent cohort of metastatic CRC patients, our previous results demonstrating that overexpression of HLA-E/β2m by tumor cells (10), as well as the high density of CD94+ TILs (11), in primary tumors at diagnosis predict an unfavorable prognosis. This evidence concerns the gene KLRD1 and neoplasm.