Marlene and Stewart Greenebaum Comprehensive Cancer Center, University of Maryland, Baltimore, MD, USA.
Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Johns Hopkins University, Baltimore, MD, USA.
Nat Immunol. 2024 Nov;25(11):2110-2123. doi: 10.1038/s41590-024-01992-w. Epub 2024 Oct 25.
Tertiary lymphoid structures (TLS) are associated with improved response in solid tumors treated with immune checkpoint blockade, but understanding of the prognostic and predictive value of TLS and the circumstances of their resolution is incomplete. Here we show that in hepatocellular carcinoma treated with neoadjuvant immunotherapy, high intratumoral TLS density at the time of surgery is associated with pathologic response and improved relapse-free survival. In areas of tumor regression, we identify a noncanonical involuted morphology of TLS marked by dispersion of the B cell follicle, persistence of a T cell zone enriched for T cell-mature dendritic cell interactions and increased expression of T cell memory markers. Collectively, these data suggest that TLS can serve as both a prognostic and predictive marker of response to immunotherapy in hepatocellular carcinoma and that late-stage TLS may support T cell memory formation after elimination of a viable tumor.
三级淋巴结构 (TLS) 与接受免疫检查点阻断治疗的实体瘤的疗效改善相关,但对于 TLS 的预后和预测价值以及其消退情况的理解尚不完全。在这里,我们发现,在接受新辅助免疫治疗的肝细胞癌中,手术时肿瘤内高 TLS 密度与病理反应和无复发生存期改善相关。在肿瘤消退区域,我们鉴定出一种非典型的 TLS 退化形态,其特征是 B 细胞滤泡弥散、富含 T 细胞-成熟树突状细胞相互作用的 T 细胞区的持续存在以及 T 细胞记忆标志物的表达增加。总的来说,这些数据表明,TLS 可以作为肝细胞癌对免疫治疗反应的预后和预测标志物,晚期 TLS 可能在消除存活肿瘤后支持 T 细胞记忆形成。
Front Immunol. 2025-6-4
Int Immunopharmacol. 2025-8-28
Nat Aging. 2025-8
Immunol Rev. 2025-7
Immunol Rev. 2025-7
Nat Rev Cancer. 2025-5-16
Immunity. 2023-10-10
N Engl J Med. 2023-3-2
N Engl J Med. 2022-5-26
Front Pharmacol. 2022-2-25