Fig. 1: T cell characteristics associated with the efficacy of CAR-T cell therapy in hematological malignancies.

a T_EX cells form during cancer where antigen persists, and are characterized by loss of cytokine production, poor proliferation, and high expression of inhibitory receptors. CAR-T_EX have similar features, and the exhaustion molecules are related to poor efficacy of CAR-T therapy. b T cells linearly differentiate to various memory subsets following cancer antigen stimulation, losing proliferation potential, but gaining effector functions. In CAR-T cell therapy, T-cell products with early memory phenotypes exhibit superior proliferative capacity, anti-tumor ability, and persistence. c The metabolic phenotypes and memory status of T cells are interconnected. T_N and early memory T cells mainly rely on OXPHOS, but shift to glycolysis as they differentiate into T_EFF. T_EM utilizes both OXPHOS and glycolysis, and can rapidly increase glycolytic activity to support effector functions. d T_REG suppress the function of CAR-T cells, and their numbers are negatively correlated with treatment response and survival. e A defined ratio of CD4⁺/CD8⁺ CAR-T cells improves therapeutic response and reduces toxicity in CAR-T cell-treated patients. f Senescent CAR-T cells exhibit terminal differentiation, loss of proliferative capacity, and compromised cytotoxic function. g TCR repertoire can be used as a surrogate for T-cell clonotype and expansion. A highly diverse baseline TCR repertoire is associated with favorable responses and improved survival outcomes in CAR-T cell therapy. CAR, chimeric antigen receptor; T_EX, exhausted T cells; T_N, naïve T cells; T_SCM, T memory stem cells; T_CM, central memory T cells; T_EM, effector memory T cells; T_EFF, effector T cells; T_REG, regulatory T cells; T_SEN, senescent T cells; OXPHOS, oxidative phosphorylation; TCR, T cell receptor.