抗体依赖性细胞介导的细胞毒性
细胞毒性T细胞
白细胞介素21
肿瘤微环境
癌症研究
免疫学
白细胞介素2受体
CD20
T细胞
生物
免疫系统
抗体
体外
单克隆抗体
生物化学
作者
Jyoti Arora,Sabarish Ayyappan,Chaobo Yin,Brian J. Smith,Caitlin D Lemke-Miltner,Zhaoming Wang,Umar Farooq,George J. Weiner
出处
期刊:Blood
[American Society of Hematology]
日期:2024-03-08
标识
DOI:10.1182/blood.2023023370
摘要
Rituximab (RTX) and other monoclonal antibodies (mAbs) that bind directly to malignant cells are of great clinical value but are not effective for all patients. A major mechanism of action of RTX is antibody dependent cellular cytotoxicity (ADCC) mediated by NK cells. Prior in vitro studies in our laboratory demonstrated that T cells contribute to maintaining the viability and cytotoxic potential of NK cells activated by anti-CD20-coated target B cells. Here, we conducted studies using a novel mouse model and clinical correlative analysis to assess whether T cell help contributes to RTX-mediated NK cell ADCC in the tumor microenvironment (TME) in vivo. A humanized mouse model was developed using Raji lymphoma cells and normal donor peripheral blood mononuclear cells that allows for control of T cell numbers in the lymphoma TME. In this model, NK cell viability, CD16 and CD25 expression dropped following RTX in the absence of T cells but increased in the presence of T cells. RTX therapy was more effective when T cells were present and was ineffective when NK cells were depleted. In indolent lymphoma patients, fine needle aspirates were obtained prior to and approximately one week after treatment with a RTX-containing regimen. There was a strong correlation between CD4+ T cells as well as total T cells in the pre-therapy TME, and an increase in NK cell CD16 and CD25 expression following RTX. We conclude that T cell help in the TME enhances RTX-mediated NK cell viability and ADCC.
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