HAVCR2 and cancer: To model T cell exhaustion and verify whether the lack of TIM-3-, LAG-3- or 2B4 overcome the loss of function of tumor-specific T cells, we adapted a chronic stimulation protocol (51–53) and daily stimulated TCRED-IRCOMP and TCRED-IRKO T cells with U266 or MM1.s A2posESO-1pos cancer cells, and we assessed the anti-tumor response 2 to 3 weeks later (Figure 4A).