CELL INTELLIGENCE · 肿瘤细胞治疗研究

ABSTRACT: Patients treated with chimeric antigen receptor T-cell (CAR-T) therapy are subject to profound immunosuppression. Dynamics of immune reconstitution (IR) and impacts of IR on outcomes following infusion across CAR-T products are not well understood. In this study, we profiled IR in 263 patients with relapsed/refractory large B-cell lymphoma receiving CAR-T therapy (axicabtagene ciloleucel 44. 9%, lisocabtagene maraleucel 30. 4%, and tisagenlecleucel 24. 7%). Following infusion, patients remain persistently immunosuppressed, with 48. 1% having CD4+ T-cell counts <200/ L and the median CD3-CD19+ B-cell counts remaining zero through 1 year after CAR-T therapy.

IR differences exist by product, with the fastest CD4+ T-cell recovery seen for tisagenlecleucel, driven primarily by more rapid recovery of the CD4+CCR7 CD45RA effector memory subset. NK cell, but not CD4+ T cell, recovery is significantly associated with favorable progression-free (HR, 0. 65; 95% confidence interval, 0. 48 0.

88) and overall survival (HR, 0. 64; 95% confidence interval, 0. 44 0. 92) and inversely correlated with inflammatory markers measured at the time of infusion. SIGNIFICANCE: This study reveals differences in IR patterns after CAR-T therapy in patients with large B-cell lymphoma, with early NK cell recovery emerging as a key predictor of survival.

These findings provide potential future avenues of research for improving patient outcomes and tailoring post-therapy management strategies to mitigate relapse risk.