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 transcriptomics reveals tumor-infiltrating B cell function after neoadjuvant pembrolizumab and chemotherapy in non-small cell lung cancer.
Single-cell transcriptomics reveals tumor-infiltrating B cell function after neoadjuvant pembrolizumab and chemotherapy in non-small cell lung cancer.
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非小细胞肺癌(NSCLC)是最普遍的肺癌亚型。近期研究表明,免疫检查点抑制剂在可切除NSCLC中取得了良好的临床获益;然而,相关机制仍不清楚。T细胞在抗肿瘤免疫中的作用受到了广泛关注,而肿瘤浸润B细胞(TIBs)在NSCLC中的抗肿瘤效应仍知之甚少。在此,我们对来自12例IIIA期NSCLC患者的免疫细胞进行了单细胞RNA测序分析,以研究新辅助化疗免疫治疗后的B细胞亚型及其功能。我们证实了4种B细胞亚型的同时存在。其中,记忆B细胞被发现与新辅助化疗免疫治疗的阳性治疗效果相关。此外,我们发现G蛋白偶联受体183在记忆B细胞中最为普遍,并与阳性治疗反应相关。在另一个由22例初治患者和30例接受新辅助化疗免疫治疗的IIIA/IIIB期NSCLC患者组成的队列中,多重免疫荧光和流式细胞术实验验证了这些发现。总体而言,我们的分析揭示了TIBs的功能及其对NSCLC临床治疗的潜在影响。
Non-small cell lung cancer (NSCLC) is the most pervasive lung cancer subtype. Recent studies have shown that immune checkpoint inhibitors achieved favorable clinical benefits in resectable NSCLC; however, the associated mechanism remains unclear. The role of T cells in antitumor immunity has received considerable attention, while the antitumor effects of tumor-infiltrating B cells (TIBs) in NSCLC remain poorly understood.
Here, we conducted a single-cell RNA sequencing analysis of immune cells isolated from 12 patients with stage IIIA NSCLC to investigate B cell subtypes and their functions following neoadjuvant chemoimmunotherapy.
We confirmed the simultaneous existence of the 4 B cell subtypes. Among them, memory B cells were found to be associated with a positive therapeutic effect to neoadjuvant chemoimmunotherapy.
Furthermore, we found that G protein-coupled receptor 183 was most prevalent in memory B cells and associated with a positive therapeutic response. Multiplex immunofluorescence and flow cytometry experiments in an additional cohort of 22 treatment-naïve and 30 stage IIIA/IIIB NSCLC patients treated with neoadjuvant chemoimmunotherapy verified these findings.
Overall, our analysis revealed the functions of TIBs and their potential effect on clinical treatment in NSCLC.
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