文章：

胰腺导管腺癌中三级淋巴结构与浆细胞的异质性：有无淋巴结转移的对比研究

Heterogeneity of Tertiary Lymphoid Structures and Plasma Cells in PDAC with and Without Lymph Node Metastasis

原文发布日期：9 September 2025

DOI: 10.3390/cancers17182949

类型: Article

开放获取: 是

英文摘要：

Background/Objectives: TLSs are favorable PDAC prognostic biomarkers. However, the mechanisms underlying TLSs formation and their contribution to the humoral antitumor immune response remain poorly understood.Methods: We used mIF staining combined with AI-based pathological image analysis software to assess the heterogeneity in the distribution of TLSs, B cells, plasma cells, and tumor cells between N0 and N1/2 PDAC. Three scRNA-seq datasets and the TCGA-PAAD database were utilized to investigate the functional heterogeneity in B cells and plasma cells.Results: The TLS area and maturity in N0 PDAC were higher than those in N1/2 PDAC. The densities of memory B cells and germinal-center B cells in intratumoral mTLSs, as well as plasma cells in stromal imTLSs, were associated with the density of intratumoral plasma cells. Moreover, plasma cells in N0 PDAC exhibited stronger IgG antibody production than those in N1/2 PDAC. IgG+tumor cells congregated within 40 μm of IgG+plasma cells, forming an IgG+plasma cell-related immune hotspot in N0 PDAC, which was not observed in N1/2 PDAC. The distance between IgG+plasma cells and the nearest IgG+tumor cells was a new prognosis biomarker.Conclusions: The TLS formation and development in N0 PDAC were better than those in N1/2 PDAC, and there is an IgG+plasma cell-related immune hotspot in N0 PDAC. The TLS area and maturity and the distance between IgG+plasma cells and the nearest IgG+tumor cells could be PDAC prognostic biomarkers.

摘要翻译： 

背景/目的：三级淋巴结构（TLSs）是胰腺导管腺癌（PDAC）的有利预后生物标志物。然而，TLSs形成的机制及其在体液抗肿瘤免疫应答中的作用仍不清楚。方法：我们采用多重免疫荧光（mIF）染色结合基于人工智能的病理图像分析软件，评估了N0期与N1/2期PDAC之间TLSs、B细胞、浆细胞和肿瘤细胞分布的异质性。利用三个单细胞RNA测序（scRNA-seq）数据集和TCGA-PAAD数据库，研究了B细胞和浆细胞的功能异质性。结果：N0期PDAC的TLS面积和成熟度均高于N1/2期PDAC。瘤内成熟TLS（mTLSs）中的记忆B细胞和生发中心B细胞密度，以及基质内瘤内TLS（imTLSs）中的浆细胞密度，与瘤内浆细胞密度相关。此外，N0期PDAC中的浆细胞表现出比N1/2期PDAC更强的IgG抗体产生能力。在N0期PDAC中，IgG+肿瘤细胞聚集在IgG+浆细胞40微米范围内，形成了一个IgG+浆细胞相关的免疫热点，这在N1/2期PDAC中未观察到。IgG+浆细胞与最近IgG+肿瘤细胞之间的距离是一个新的预后生物标志物。结论：N0期PDAC的TLS形成和发展优于N1/2期PDAC，并且在N0期PDAC中存在一个IgG+浆细胞相关的免疫热点。TLS面积和成熟度，以及IgG+浆细胞与最近IgG+肿瘤细胞之间的距离，可作为PDAC的预后生物标志物。

原文链接：

Heterogeneity of Tertiary Lymphoid Structures and Plasma Cells in PDAC with and Without Lymph Node Metastasis