CD28 and colorectal carcinoma: First, CD3 on CD28- CD8+ T cell mediated the pathway from 16a-hydroxy DHEA 3-sulfate to CRC with a mediation effect of -0.014 (95% CI [-0.043, 0.014], P = 0.048, Table 1, Figure 6), accounting for -22.06% of the total effect.