不适合移植的大 B 细胞淋巴瘤二线使用 axicabtagene ciloleucel:ALYCANTE 最终分析
Second-line axicabtagene ciloleucel in large B-cell lymphoma ineligible for transplantation: ALYCANTE final analysis.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Patient parameters and response after administration of rituximab in pediatric mature B-cell non-Hodgkin lymphoma.
Patient parameters and response after administration of rituximab in pediatric mature B-cell non-Hodgkin lymphoma.
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利妥昔单抗治疗对患者免疫应答的突出效应,有助于理解肿瘤防御机制与效应功能背后的生物学机制。
成熟型侵袭性B细胞淋巴瘤是儿童和青少年非霍奇金淋巴瘤(NHL)中占比超过一半的异质性恶性肿瘤。过去数十年,随着多药化疗方案不断优化,总生存率已提高至80%至90%;但仍需新的治疗策略进一步改善生存。目前临床试验正在评估利妥昔单抗在儿童患者中的治疗作用,而其体内作用机制尚未完全阐明。
采用流式细胞术,在利妥昔单抗治疗前及治疗第5天检测参与肿瘤防御的效应分子,并通过ELISA测量血清利妥昔单抗水平。
研究评估了可能影响治疗反应的患者特征及其与利妥昔单抗给药和血清药物浓度的关系。治疗后,单核细胞亚群的Fc受体II(FcγRII)水平下降,而Fc受体I(FcγRI)表达显著升高。血清促炎标志蛋白S100A8/A9和S100A12水平显著下降,从治疗前整体偏高的炎症状态恢复至正常水平。治疗后,CD57、穿孔素和颗粒酶B表达下降,表明NK细胞群的细胞毒性减弱。
利妥昔单抗对患者免疫应答的上述影响,有助于理解肿瘤防御机制和效应功能的生物学基础。后续研究若能进一步证实这些新发现,或可将其转化为临床实践,改善成熟型侵袭性B细胞淋巴瘤儿童患者的治疗。
Mature aggressive B-cell lymphomas are heterogenous malignancies that make up more than half of all diagnosed non-Hodgkin lymphoma in children and adolescents. The overall survival rate increased over the last decades to 80%-90% due to fine tuning of polychemotherapy. However, new therapeutic implications are needed to further increase the overall survival. Current clinical trials analyze the therapeutic effect of rituximab in pediatric patients, while the mechanism of action in vivo is still not fully understood.
Effector molecules important for tumor defense were analyzed before and at day 5 after rituximab treatment via flow cytometry. Serum rituximab levels were measured with an ELISA.
We evaluated patient parameters that may affect treatment response in relation to rituximab administration and serum rituximab levels. We indeed found a reduction of Fc receptor (Fc R) II levels after rituximab treatment in monocyte subtypes, whereas Fc RI expression was significantly increased. Serum levels of proinflammatory marker proteins S100A8/A9 and S100A12 significantly decreased after treatment to normal levels from an overall proinflammatory state before treatment. CD57, perforin, and granzyme B expression decreased after treatment, comprising a less cytolytic natural killer (NK) cell population.
The highlighted effects of rituximab treatment on patient's immune response help in understanding the biology behind tumor defense mechanisms and effector function. After subsequent studies, these novel insights might be translated into patient care and could contribute to improve treatment of pediatric patients with mature aggressive B-cell lymphoma.
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