RNF43 p.G659fs 通过 PI3K/AKT/mTOR 信号通路和 HLA-E 上调导致 MSI-high 结直肠癌中 NK 细胞功能障碍
RNF43 p.G659fs leads to natural killer cell dysfunction in MSI-high colorectal cancer through PI3K/AKT/mTOR signaling and HLA-E up-regulation.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Blinatumomab differentially modulates peripheral blood and bone marrow immune cell repertoire: A Campus ALL study.
Blinatumomab differentially modulates peripheral blood and bone marrow immune cell repertoire: A Campus ALL study.
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Blinatumomab是首个获批用于复发/难治性B细胞前体急性淋巴细胞白血病(B-ALL)的双特异性T细胞衔接器。尽管临床结果显著,但blinatumomab对宿主免疫细胞库的影响尚未完全阐明。
在本研究中,我们表征了blinatumomab治疗后的外周血(PB)免疫细胞库,并首次表征了骨髓(BM)免疫细胞库。29例B-ALL患者根据临床实践接受了blinatumomab治疗。采用深度多参数流式细胞术表征第一个治疗周期中的淋巴亚群。Blinatumomab诱导了PB效应T细胞亚群和Treg细胞的短暂重分布,同时伴有细胞毒性NK细胞的持续增加,这与PB CD4和CD8 T细胞亚群上免疫检查点受体的短暂上调以及抑制性Treg细胞上CD39表达的短暂上调相关。
值得注意的是,BM免疫T细胞亚群显示出更广泛的治疗后改变,包括与T细胞耗竭表型相关的标志物的调节。总之,我们的研究表明,blinatumomab对PB和BM免疫细胞库的调节存在差异,这可能具有相关的临床治疗意义。
Blinatumomab is the first bi-specific T-cell engager approved for relapsed or refractory B-cell precursor acute lymphoblastic leukaemia (B-ALL). Despite remarkable clinical results, the effects of blinatumomab on the host immune cell repertoire are not fully elucidated. In the present study, we characterized the peripheral blood (PB) and, for the first time, the bone marrow (BM) immune cell repertoire upon blinatumomab treatment. Twenty-nine patients with B-ALL received blinatumomab according to clinical practice.
Deep multiparametric flow cytometry was used to characterize lymphoid subsets during the first treatment cycle. Blinatumomab induced a transient redistribution of PB effector T-cell subsets and Treg cells with a persistent increase in cytotoxic NK cells, which was associated with a transient upregulation of immune checkpoint receptors on PB CD4 and CD8 T-cell subpopulations and of CD39 expression on suppressive Treg cells.
Of note, BM immune T-cell subsets showed a broader post-treatment subversion, including the modulation of markers associated with a T-cell-exhausted phenotype.
In conclusion, our study indicates that blinatumomab differentially modulates the PB and BM immune cell repertoire, which may have relevant clinical implications in the therapeutic setting.
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