CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题：Tertiary Lymphoid Structures in Pancreatic Cancer are Structurally Homologous, Share Gene Expression Patterns and B-cell Clones with Secondary Lymphoid Organs, but Show Increased T-cell Activation.
Tertiary Lymphoid Structures in Pancreatic Cancer are Structurally Homologous, Share Gene Expression Patterns and B-cell Clones with Secondary Lymphoid Organs, but Show Increased T-cell Activation.
分数与星级只用于站内排序 —— 不代表疗效、安全性或个人适用性。
癌症中的三级淋巴结构（TLS）被认为是类似于次级淋巴器官（SLO）中淋巴滤泡的异位免疫激活热点。本研究阐明了胰腺导管腺癌（PDAC）中TLS与SLO的共有特征及TLS/SLO特异性特征。在110例未经治疗的PDAC样本中，TLS丰度与更优的生存期及T细胞丰度相关，凸显了其临床相关性。免疫荧光显微镜鉴定出TLS与SLO之间的结构同源性。在激光显微切割的TLS与配对SLO的RNA表达分析中，我们观察到免疫相关基因簇的表达模式在很大程度上重叠，但T细胞和补体相关基因的表达模式存在差异。TLS中的免疫细胞表达生发中心形成的关键标志物。TLS数量高的患者中肿瘤引流淋巴结激活增加，凸显了这些肿瘤相关结构与全身免疫反应的相关性。与此一致，我们在TLS和SLO中鉴定出扩增的B细胞受体克隆型存在重叠，提示两个区域之间存在活跃的交互对话。
我们得出结论，利用TLS介导的抗肿瘤免疫反应的联合治疗策略可能改善PDAC对免疫治疗的敏感性。
Tertiary lymphoid structures (TLS) in cancer are considered ectopic hotspots for immune activation that are similar to lymphoid follicles in secondary lymphoid organs (SLO).
This study elucidates shared and TLS/SLO-specific features in pancreatic ductal adenocarcinoma (PDAC). TLS abundance was related to superior survival and T-cell abundance in 110 treatment-naïve PDAC samples, underlining their clinical relevance. Immunofluorescence microscopy identified structural homologies between TLSs and SLOs. In RNA expression analyses of laser-microdissected TLSs and paired SLOs, we observed largely overlapping expression patterns of immune-related gene clusters but distinct expression patterns of T-cell and complement-associated genes.
Immune cells in TLS expressed essential markers of germinal center formation. Increased activation of tumor-draining lymph nodes in patients with high numbers of TLSs highlights the relevance of these tumor-related structures to systemic immune response. In line with this, we identified an overlap of expanded B-cell receptor clonotypes in TLSs and SLOs, which suggests a vivid cross-talk between the two compartments.
We conclude that combined therapeutic approaches exploiting TLS-mediated antitumor immune responses may improve susceptibility of PDAC to immunotherapy.
MEMBER ACCOUNT
登录成功会直接打开下一页。
