评估前哨淋巴结切除对宫颈癌的影响:免疫遗传学视角 - SENTICOL 辅助研究。
Assessing the implications of sentinel lymph node removal in cervical cancer: an immunogenetic perspective - a SENTICOL ancillary study.
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
来源:
Journal for ImmunoTherapy of Cancer
摘要:
宫颈癌的淋巴扩散主要从前哨淋巴结(SLN)开始,这凸显了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仍有待探索。我们的研究旨在使用 Nanostring RNA 阐明阴性 SLN 与阳性 SLN 和非 SLN 相比的免疫细胞群及其在免疫基因表达谱中的作用序列分析。我们对 nCounter PanCancer Immune Profiling Panel 中 685 个内源基因的 log2 归一化表达进行了主成分分析,然后评估了基因的差异表达和免疫细胞类型丰度。我们发现各组之间基因表达存在显着差异,阴性 SLN 显示与肿瘤浸润免疫细胞(特别是先天细胞群)相关的基因过度表达。他们还证明了参与抗原呈递和 T 细胞启动的基因的上调。相比之下,阳性前哨淋巴结在调控网络中丰富,表明它们在免疫逃避中的潜在作用。阴性 SLN 和非 SLN 的比较揭示了先天性和适应性免疫细胞类型的增加,强调了 T 细胞对肿瘤抗原的持续反应。我们的研究结果强调了阴性 SLN 中特定的免疫遗传学表型特征,强调了它们在初始抗癌反应中的关键作用,免疫监视和原发性宫颈肿瘤免疫耐受的传播。这些结果凸显了 SLN 作为免疫治疗策略新靶点的潜力,并强调了新成像方法对于准确识别 SLN 状态而无需切除的重要性。未来的研究需要进一步了解 SLN 内的免疫相互作用及其对宫颈癌进展的影响。© 作者(或其雇主)2024。根据 CC BY-NC 允许重复使用。不得商业再利用。请参阅权利和权限。由英国医学杂志出版。
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.© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.