肿瘤细胞治疗研究
英文原题：Microwave ablation of non-small cell lung cancer enhances local T-cell abundance and alters monocyte interactions.
Microwave ablation of non-small cell lung cancer enhances local T-cell abundance and alters monocyte interactions.
MWA 增加了局部 T 细胞丰度并改变了单核细胞相互作用，从而重塑了肿瘤微环境。本研究为探究可能导致 NSCLC 中 MWA 诱导免疫反应的失调基因奠定了基础。关于该主题的已知信息：热消融可能通过激活癌症免疫周期中的多个步骤来改变患者的免疫特征。然而，NSCLC 行 MWA 后免疫细胞群的变化尚未被充分报道。MWA 后，观察到肿瘤内单核细胞与 T 细胞之间的相互作用增加，这促进了抗肿瘤免疫。本研究可能如何影响研究、实践或政策：当前研究阐明了 NSCLC 中 MWA 引起的全身免疫反应，这可能有助于识别参与 MWA 引起免疫反应的失调基因。
微创热疗在非小细胞肺癌（NSCLC）治疗中展现出巨大前景。然而，NSCLC微环境中微波消融（MWA）后免疫细胞群的变化尚未完全阐明。
本研究旨在识别NSCLC微环境中MWA后免疫细胞群体的变化，并分析免疫细胞中失调的基因。
患者接受分次MWA，分两次治疗，间隔3周。在每次分次MWA操作前，于同一部位通过空芯针活检获取肿瘤活检样本，并用于10x Genomics流程的单细胞RNA测序。
MWA后共鉴定出9种主要细胞类型，包括中性粒细胞、T细胞、B细胞、单核细胞、上皮细胞、软骨细胞、巨噬细胞、组织干细胞和内皮细胞。MWA后，肿瘤组织中T细胞比例增加。MWA在单细胞水平改变了每个细胞簇的基因表达。细胞轨迹分析显示，起始点的细胞最像辅助性T细胞、初始T细胞和调节性T细胞；随后它们发育为无反应性T细胞、滤泡性T细胞、自然杀伤T细胞、T记忆细胞和耗竭T细胞，最终终止为γδ T细胞和细胞毒性T细胞。此外，MWA后，单核细胞与T细胞（或B细胞）之间鉴定出更多相互作用。
BACKGROUND: Minimally invasive thermal therapies show great prospect in non-small cell lung cancer (NSCLC) treatment. However, changes in immune cell populations following microwave ablation (MWA) in NSCLC microenvironment are not fully revealed. OBJECTIVE: The present study was conducted to identify changes in immune cell populations and analyse dysregulated genes in immune cells after MWA in NSCLC microenvironment. METHODS: The patients received fractionated MWA in two treatments separated by 3 weeks. Tumor biopsy samples were obtained through core-needle biopsy before each fractionated MWA procedure at the same site and used for single-cell RNA sequencing with the 10x Genomics pipeline. RESULTS: A total of 9 major cell types were identified after MWA, which include neutrophils, T cells, B cells, monocytes, epithelial cells, chondrocytes, macrophages, tissue stem cells, and endothelial cells. After MWA, the tumor tissue exhibited an increased proportion of T cells. MWA altered gene expression in each cell cluster at the single-cell level. Cell trajectory analysis revealed that the cells at the starting point were most like T helper cells, naïve T cells, and regulatory T cells; they then developed into anergic T cells, T follicular cells, natural killer T cells, T memory cells, and exhausted T cells, and finally ended as γδ T cells and cytotoxic T cells. Moreover, after MWA, more interaction between monocytes and T cells (or B cells) were identified. CONCLUSIONS: MWA increases local T-cell abundance and alters monocyte interactions, thereby reshaping the tumor microenvironment. This study lays a foundation for investigating dysregulated genes that may contribute to the MWA-induced immune response in NSCLC. WHAT IS ALREADY KNOWN ON THIS TOPIC: Thermal ablation may change the immune profiles of patients by activating various steps in the cancer immunity cycle. However, changes in immune cell populations following MWA of NSCLC have not been fully reported. WHAT THIS STUDY ADDS: After MWA, an increase in interactions between monocytes and T cells intratumorally was observed, which promoted antitumor immunity. HOW THIS STUDY MIGHT AFFECT RESEARCH, PRACTICE OR POLICY: The current study illuminates the MWA-caused systemic immune response in NSCLC, which may help to identify the dysregulated genes involved in the MWA-caused immune response.
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