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评估前哨淋巴结在宫颈癌中的含义:一种免疫遗传学观点 - 哨兵辅助研究

Assessing the implications of sentinel lymph node removal in cervical cancer: an immunogenetic perspective - a SENTICOL ancillary study

影响因子:10.60000
分区:医学1区 Top / 免疫学1区 肿瘤学2区
发表日期:2024 Jul 15
作者: Gaurav Thareja, Anna Salvioni, Françoise Lauzeral-Vizcaino, Najeeb Halabi, Eliane Mery-Lamarche, Noemie Thebault, Clara-Maria Scarlata, Marie Michelas, Anne-Sophie Navarro, Gwenaël Ferron, Fabrice Lecuru, Patrice Mathevet, Jonathan Khalifa, Maha Ayyoub, Arash Rafii, Alejandra Martinez

摘要

宫颈癌的淋巴扩散主要始于前哨淋巴结(SLN),强调了它们在疾病转移中的关键作用。但是,这些节点的免疫基因表达谱和免疫调节机制尚未探索。我们的研究旨在阐明与阳性SLN和非SLNS的负面SLN和非SLNS的免疫细胞群体及其在免疫基因表达中的作用。我们对Ncounter Pancancer免疫分析面板中685个内源基因的Log2归一化表达进行了主要成分分析,然后评估了基因的差异表达和免疫细胞类型丰度的差异表达。我们在基因表达中发现了基因表达的显着变化,在基因之间表现出了负面的基因与细胞相关细胞的过度表达,这些细胞表现出了与肿瘤的特定细胞的过度表达。他们还证明了参与抗原表现和T细胞启动的基因的上调。相比之下,阳性SLN在调节网络中富集,这表明它们在免疫逃避中的潜在作用。负SLN和非SLN的比较表明,先天性和适应性免疫细胞类型增加,强调了对肿瘤抗原的持续T细胞反应。我们的发现强调了在初始抗癌反应,免疫抗耐受性和perpagianter canneme nume nume n nume neme neme neme neme neme nume nume neme nume nume neme nume andune n nume n neme n neme n nemene n nemene n n plyeme n n plyemene n name n nemene n n plyer的癌症的特定免疫遗传表型概况。这些结果突出了SLN作为免疫疗法策略的新目标的潜力,并强调了新成像方法对于准确识别SLN状态而无需去除的重要性。需要进行未来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。

Abstract

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.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.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.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.