一种用于克服非小细胞肺癌治疗中抗原异质性的多靶向 CAR-T 细胞平台
A Multi-Targeting Chimeric Antigen Receptor-T Cell Platform to Overcome Antigen Heterogeneity in the Treatment of Non-Small Cell Lung Cancer.
这些发现支持采用多靶点CAR-T 策略来应对NSCLC及可能其他实体瘤中的抗原异质性。
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Single-cell study reveals early alterations in peripheral blood immune responses at day 7 following microwave ablation for lung cancer.
Single-cell study reveals early alterations in peripheral blood immune responses at day 7 following microwave ablation for lung cancer.
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这项初步研究提供了初步的单细胞证据,提示 MWA 如何重塑 LC 中的免疫景观,但这些发现需要在更大的队列中进一步验证。
肺癌(LC)是癌症相关死亡的主要原因。微波消融(MWA)是一种有前景的局部治疗手段,但其对全身免疫的影响尚不清楚。
在这项探索性初步研究中,通过单细胞RNA测序(scRNA-seq)分析了两名LC患者MWA前后的配对外周血样本。研究了细胞组成、功能状态和细胞间通讯。通过RT-qPCR和ELISA测定法检测了源自PBMCs的CD8+T细胞中细胞毒性因子(包括GZMB、TNF-α和IFN-γ)的表达水平。
scRNA-seq鉴定出9种免疫细胞类型。MWA后,单核细胞和NKT细胞增加。功能变化包括T细胞细胞毒性增强、促炎性单核细胞活化以及抗肿瘤中性粒细胞分化。细胞通讯分析突出显示了T细胞与单核细胞/中性粒细胞之间富集的LGALS9-CD45和RETN-CAP1相互作用。体外细胞实验显示,MWA处理后CD8+ T细胞中细胞毒性因子(GZMB、TNF-α和IFN-γ)的表达显著上调。
Lung cancer (LC) is a leading cause of cancer-related death. Microwave ablation (MWA) is a promising local therapy, but its impact on systemic immunity remains unclear.
In this exploratory pilot study, paired peripheral blood samples from two LC patients pre- and post-MWA were analyzed by single-cell RNA sequencing (scRNA-seq). Cell composition, functional states, and intercellular communication were investigated. The expression levels of cytotoxic factors including GZMB, TNF-α, and IFN-γ in CD8 + T cells derived from PBMCs were determined via RT-qPCR and ELISA assays.
scRNA-seq identified 9 immune cell types. Post-MWA, monocytes and NKT cells increased. Functional changes included enhanced T cell cytotoxicity, activated pro-inflammatory monocytes, and anti-tumor neutrophil differentiation. Cell communication analysis highlighted enriched LGALS9-CD45 and RETN-CAP1 interactions between T cells and monocytes/neutrophils. In vitro cellular assays revealed that the expression of cytotoxic factors (GZMB, TNF-α, and IFN-γ) in CD8 + T cells was significantly upregulated following MWA treatment.
This pilot study provides preliminary single-cell evidence suggesting how MWA remodels the immune landscape in LC, however, these findings require further validation in larger cohorts.
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