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Abstract：
BACKGROUND: Cervical cancer\'s lymphatic spread primarily begins from the sentinel lymph nodes (SLNs), underlining their pivotal role in disease metastasis. However, these nodes\' immune gene expression profiles and immunoregulation mechanisms have yet to be explored.
METHODS: Our study aimed to elucidate the immune cell populations and their roles in the immune gene expression profile of negative SLNs compared with positive SLNs and non-SLNs using Nanostring RNA seq analysis. We performed a principal component analysis on the log2 normalized expression of 685 endogenous genes in the nCounter PanCancer Immune Profiling Panel, followed by an assessment of the differential expression of genes and immune cell type abundance.
RESULTS: We found significant variations in gene expression among the groups, with negative SLNs displaying overexpression of genes related to tumor-infiltrating immune cells, specifically innate cell populations. They also demonstrated the upregulation of genes involved in antigen presentation and T-cell priming. In contrast, positive SLNs were enriched in regulatory networks, suggesting their potential role in immune evasion. A comparison of negative SLNs and non-SLNs revealed increased innate and adaptive immune cell types, underscoring the ongoing T cell response to tumor antigens.
CONCLUSIONS: Our findings underscore a specific immunogenetic phenotype profile in negative SLNs, emphasizing their crucial role in the initial anticancer response, immunosurveillance, and the propagation of immune tolerance from the primary cervical tumor. These results highlight the potential of SLNs as a novel target for immunotherapy strategies and underscore the importance of new imaging methods for accurately identifying SLN status without removal. Future investigations are needed to understand further the immunological interplay within SLNs and their influence on cervical cancer progression.
METHODS: Our study aimed to elucidate the immune cell populations and their roles in the immune gene expression profile of negative SLNs compared with positive SLNs and non-SLNs using Nanostring RNA seq analysis. We performed a principal component analysis on the log2 normalized expression of 685 endogenous genes in the nCounter PanCancer Immune Profiling Panel, followed by an assessment of the differential expression of genes and immune cell type abundance.
RESULTS: We found significant variations in gene expression among the groups, with negative SLNs displaying overexpression of genes related to tumor-infiltrating immune cells, specifically innate cell populations. They also demonstrated the upregulation of genes involved in antigen presentation and T-cell priming. In contrast, positive SLNs were enriched in regulatory networks, suggesting their potential role in immune evasion. A comparison of negative SLNs and non-SLNs revealed increased innate and adaptive immune cell types, underscoring the ongoing T cell response to tumor antigens.
CONCLUSIONS: Our findings underscore a specific immunogenetic phenotype profile in negative SLNs, emphasizing their crucial role in the initial anticancer response, immunosurveillance, and the propagation of immune tolerance from the primary cervical tumor. These results highlight the potential of SLNs as a novel target for immunotherapy strategies and underscore the importance of new imaging methods for accurately identifying SLN status without removal. Future investigations are needed to understand further the immunological interplay within SLNs and their influence on cervical cancer progression.
摘要：
背景：宫颈癌的淋巴扩散主要从前哨淋巴结（SLN）开始，强调它们在疾病转移中的关键作用。然而,这些节点的免疫基因表达谱和免疫调节机制还有待探索。
方法：我们的研究旨在使用NanostringRNAseq分析阐明免疫细胞群体及其在阴性SLN与阳性SLN和非SLN的免疫基因表达谱中的作用。我们对nCounterPanCancer免疫分析小组中685个内源性基因的log2标准化表达进行了主成分分析，然后评估基因和免疫细胞类型丰度的差异表达。
结果：我们发现各组基因表达存在显著差异，阴性SLN显示与肿瘤浸润免疫细胞相关的基因过表达，特别是先天细胞群。他们还证明了参与抗原呈递和T细胞引发的基因的上调。相比之下,积极的SLN在监管网络中得到了丰富，表明它们在逃避免疫中的潜在作用。阴性SLN和非SLN的比较显示先天和适应性免疫细胞类型增加，强调正在进行的T细胞对肿瘤抗原的反应。
结论：我们的发现强调了阴性SLN中特定的免疫遗传学表型谱，强调它们在初始抗癌反应中的关键作用，免疫监视,以及原发性宫颈肿瘤免疫耐受的传播。这些结果突出了SLN作为免疫治疗策略的新靶标的潜力，并强调了新的成像方法对于准确识别SLN状态而不去除的重要性。需要进行进一步的研究以进一步了解SLN内的免疫相互作用及其对宫颈癌进展的影响。
方法：我们的研究旨在使用NanostringRNAseq分析阐明免疫细胞群体及其在阴性SLN与阳性SLN和非SLN的免疫基因表达谱中的作用。我们对nCounterPanCancer免疫分析小组中685个内源性基因的log2标准化表达进行了主成分分析，然后评估基因和免疫细胞类型丰度的差异表达。
结果：我们发现各组基因表达存在显著差异，阴性SLN显示与肿瘤浸润免疫细胞相关的基因过表达，特别是先天细胞群。他们还证明了参与抗原呈递和T细胞引发的基因的上调。相比之下,积极的SLN在监管网络中得到了丰富，表明它们在逃避免疫中的潜在作用。阴性SLN和非SLN的比较显示先天和适应性免疫细胞类型增加，强调正在进行的T细胞对肿瘤抗原的反应。
结论：我们的发现强调了阴性SLN中特定的免疫遗传学表型谱，强调它们在初始抗癌反应中的关键作用，免疫监视,以及原发性宫颈肿瘤免疫耐受的传播。这些结果突出了SLN作为免疫治疗策略的新靶标的潜力，并强调了新的成像方法对于准确识别SLN状态而不去除的重要性。需要进行进一步的研究以进一步了解SLN内的免疫相互作用及其对宫颈癌进展的影响。
