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单细胞转录组学揭示非小细胞肺癌新辅助帕博利珠单抗联合化疗后肿瘤浸润 B 细胞的功能

英文原题:Single-cell transcriptomics reveals tumor-infiltrating B cell function after neoadjuvant pembrolizumab and chemotherapy in non-small cell lung cancer.

查看英文原题

Single-cell transcriptomics reveals tumor-infiltrating B cell function after neoadjuvant pembrolizumab and chemotherapy in non-small cell lung cancer.

PubMed 2024/09/02(内容时间) J Leukoc Biol Q2 · IF 3.4(JCR 2025)

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中文摘要

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。

展开英文摘要原文

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.

论文信息

作者
Hou L、Zhang S、Yu W、Yang X、Shen M、Hao X、Ren X、Sun Q
单位
National Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, No. 45 Binshui Road, Hexi District, Tianjin 300060, China.China
期刊
Journal of leukocyte biology2024 Sep 2
原文标识
PubMed 37931147 · DOI 10.1093/jleuko/qiad138