T-cell help in the tumor microenvironment enhances rituximab-mediated NK-cell ADCC

抗体依赖性细胞介导的细胞毒性 美罗华 肿瘤微环境 癌症研究 免疫学 医学 抗体 淋巴瘤 肿瘤细胞 单克隆抗体
作者
Jyoti Arora,Sabarish Ayyappan,Chaobo Yin,Bruce A. Smith,Caitlin D. Lemke,Zhao-ming Wang,Umar Farooq,George J. Weiner
出处
期刊:Blood [American Society of Hematology]
卷期号:143 (18): 1816-1824 被引量:4
标识
DOI:10.1182/blood.2023023370
摘要

Abstract 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 natural killer (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 contribute 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 and CD16 and CD25 expression dropped after 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 patients with indolent lymphoma, fine needle aspirates were obtained before and ∼1 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 pretherapy TME and an increase in NK-cell CD16 and CD25 expression after RTX. We conclude that T-cell help in the TME enhances RTX-mediated NK-cell viability and ADCC.
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