Background: Esophageal cancer remains a highly aggressive malignant tumor with poor prognosis, despite advances in combination therapies and novel immunotherapies. Tertiary lymphoid structures (TLSs), characterized by densely packed CD20+B cells in a germinal-center-like structure, have recently been recognized as immune-stimulating components within the tumor microenvironment. In contrast, cancer-associated fibroblasts (CAFs) are stromal cells expressing fibroblast-activating protein (FAP) involved in immunosuppression. Methods: In this retrospective study, 124 clinical samples from patients who underwent radical surgery for esophageal cancer at our institute were analyzed. We investigated whether TLSs could serve as a prognostic factor and examined their association with tumor microenvironment factors. Results: The presence of TLSs was an independent prognostic factor for overall and progression-free survival in multivariate analyses. A high level of TLS formation correlated with better nutritional status, fewer M2 macrophages, and greater plasma cell infiltration. Additionally, little TLS formation was observed in areas with abundant CAFs, and quantitative analyses revealed a significant negative correlation between TLSs and CAFs. Conclusions: TLSs enhance antitumor immunity via macrophages and plasma cells and can be a valuable prognostic indicator in patients undergoing surgery for esophageal cancer. Targeting CAFs may prove to be a promising therapeutic strategy to enhance tumor-immunity-related TLSs.
背景：尽管联合疗法和新型免疫疗法取得进展，食管癌仍是一种预后极差的侵袭性恶性肿瘤。三级淋巴结构（TLS）以生发中心样结构中密集的CD20+B细胞为特征，近年来被认为是肿瘤微环境中的免疫刺激组分。相比之下，癌症相关成纤维细胞（CAFs）是表达成纤维细胞活化蛋白（FAP）并参与免疫抑制的间质细胞。方法：本研究回顾性分析了本机构接受根治性手术的124例食管癌患者临床样本。我们探讨了TLS是否可作为预后因素，并研究了其与肿瘤微环境因子的关联。结果：多变量分析显示TLS的存在是总生存期和无进展生存期的独立预后因素。高水平TLS形成与更好的营养状态、更少的M2型巨噬细胞及更多的浆细胞浸润相关。此外，在CAFs富集区域观察到极少TLS形成，定量分析显示TLS与CAFs呈显著负相关。结论：TLS通过巨噬细胞和浆细胞增强抗肿瘤免疫，可作为食管癌手术患者的重要预后指标。靶向CAFs可能成为增强肿瘤免疫相关TLS的潜在治疗策略。
肿瘤(癌症)患者之家