HIF1A and neoplasm: Since hypoxia is a hallmark of solid tumors including CRC [27], where the partial oxygen pressure (pO2) drops in the tumour mass compared to normal adjacent tissues (median tumour pO2 = 19 mmHg in rectal carcinoma vs. median normal tissue pO2 = 52 mmHg) [28], and cell adaptations to hypoxia are primarily mediated by transcription factor HIF-1, we hypothesized that this transcription factor might account for the different Rai expression levels in PBLs and TILs of CRC patients.