Cheloni Giulia, Karagkouni Dimitra, Pita-Juarez Yered, Torres Daniela, Kanata Eleni, Liegel Jessica, Avigan Zachary, Saldarriaga Isabella, Chedid Georges, Rallis Kathrine, Miles Brodie, Tiwari Gayatri, Kim Jenny, Mattie Mike, Rosenblatt Jacalyn, Vlachos Ioannis S, Avigan David
Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA.
Cancer Center, Beth Israel Deaconess Medical Center, Boston, MA, USA.
Nat Commun. 2025 May 23;16(1):4819. doi: 10.1038/s41467-025-59904-x.
While Chimeric Antigen Receptor (CAR) T cell therapy may result in durable remissions in recurrent large B cell lymphoma, persistence is limited and the mechanisms underlying long-term response are not fully elucidated. Using longitudinal single-cell immunoprofiling, here we compare the immune landscape in durable remission versus early relapse patients following CD19 CAR T cell infusion in the NCT02348216 (ZUMA-1) trial. Four weeks post-infusion, both cohorts demonstrate low circulating CAR T cells. We observe that long-term remission is associated with elevated native cytotoxic and proinflammatory effector cells, and post-infusion clonotypic expansion of effector memory T cells. Conversely, early relapse is associated with impaired NK cell cytotoxicity and elevated immunoregulatory cells, potentially dampening native T cell activation. Thus, we suggest that durable remission to CAR T is associated with a distinct T cell signature and pattern of clonotypic expansion within the native T cell compartment post-therapy, consistent with their contribution to the maintenance of response.