The demonstration that Rai is upregulated in TILs of CRC patients, which are known to be dysfunctional and to express high levels of the immune checkpoint inhibitory receptor PD-1 [8], together with the negative role played by Rai in antigen-dependent T cell activation [20], led us to investigate whether Rai impacts on the signalling pathways controlling PD-1 expression. The gene discussed is PDCD1; the disease is colorectal carcinoma.