Several studies demonstrate that CD226 is required for the stimulatory effect of both TIGIT and PD-1/PD-L1 blockade.14,37,43 Furthermore, TIGIT and PD-1 receptors, through separate and distinct mechanisms, partly exert their inhibitory functions through the impairment of CD226 signaling, emphasizing the necessity for dual blockade.44 While we observed a two-fold decrease in bioavailable TIGIT in tumor infiltrating CD8+ T cells in the MC38-CEA model, we did not detect the same reduction in the TC1 model. Here, CD226 is linked to neoplasm.