肿瘤细胞治疗研究
英文原题：Durable response to CAR T is associated with elevated activation and clonotypic expansion of the cytotoxic native T cell repertoire.
虽然嵌合抗原受体（CAR）T 细胞疗法可使复发性大 B 细胞淋巴瘤获得持久缓解，但持续性有限，长期应答的机制尚未完全阐明。
嵌合抗原受体（CAR）T细胞疗法可使复发性大B细胞淋巴瘤患者获得持久缓解，但CAR T细胞持久性有限，长期应答的潜在机制尚未完全阐明。我们利用纵向单细胞免疫分析，比较NCT02348216（ZUMA-1）试验中CD19 CAR T细胞输注后持久缓解患者与早期复发患者的免疫图谱。输注4周后，两组患者循环CAR T细胞均处于低水平。我们观察到，长期缓解与天然细胞毒性和促炎效应细胞增加，以及输注后效应记忆T细胞克隆型扩增相关。相反，早期复发与NK细胞细胞毒功能受损及免疫调节细胞增多相关，后者可能抑制天然T细胞活化。因此，我们认为CAR-T治疗后的持久缓解与天然T细胞群室中独特的T细胞特征及克隆型扩增模式相关，这与其参与维持治疗应答的作用一致。
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.
MEMBER ACCOUNT
登录成功会直接打开下一页。
