Moreover, effector and naïve CD8+ T cells drive the immunological response to TCE while the exhausted CD8+ T cells are highly associated with the response failure.1040 One key challenge of CD3-TCEs in treating solid tumor is the treatment-mediated toxicity, including both cytokine release syndrome (CRS) and on-target/off-tumor toxicity.1037,1041,1042 Several strategies to overcome the adverse events of TCEs in solid tumors are under both clinical and preclinical investigations. This evidence concerns the gene CD8A and neoplasm.