Based on our previous data showing that Rai overexpression in Jurkat T cell suppresses TCR signaling and T cell activation, together with the data presented in this report showing that upregulation of Rai in human T cells correlates with enhanced PD-1 and LAG-3 expression and reduced CD8+ T degranulation, we can speculate that different levels of Rai expression in TILs among CRC patients might contribute to the different response to anti-PD-1 therapy. The gene discussed is SHC3; the disease is colorectal carcinoma.