中文摘要
三级淋巴结构(TLS)是在非淋巴组织中发育的免疫细胞有序异位淋巴簇,可促进抗原呈递、驱动细胞毒性免疫应答,并通过B细胞克隆扩增增强体液免疫。其在肿瘤微环境(TME)中的存在与患者生存期延长及对免疫检查点抑制剂(ICIs)应答改善相关,使TLS成为潜在的预测性和预后生物标志物。尽管ICIs已广泛应用于多种癌症,但其在妇科恶性肿瘤中的有效性仍然有限,包括卵巢癌(OC)——这是一种以对单药和联合ICI治疗应答不佳为特征的特别具有挑战性的疾病。有趣的是,T细胞浸润至OC的TME与无进展生存期(PFS)和总生存期(OS)改善相关,然而免疫抑制性TME常常阻碍治疗疗效,提示局部免疫微环境中的细胞活性可影响抗肿瘤免疫。本综述探讨了TLS的作用、其成熟度、功能性、鉴定及相关基因特征;在TLS形成和抗肿瘤应答中发挥作用的特定免疫细胞和细胞因子;以及其他可调控因素,包括肠道微生物群,这些因素可能通过利用TLS驱动的抗肿瘤应答来增强免疫治疗结局,从而改善OC生存。
展开英文摘要原文
Tertiary lymphoid structures (TLS) are organized ectopic lymphoid clusters of immune cells that develop in non-lymphoid tissue to promote antigen presentation, drive cytotoxic immune responses, and enhance humoral immunity via B cell clonal expansion. Their presence within the tumor microenvironment (TME) correlates with increased patient survival and an improved response to immune checkpoint inhibitors (ICIs), positioning TLS as potential predictive and prognostic biomarkers. Despite the widespread use of ICIs across various cancers, their effectiveness remains limited in gynecological malignancies, including ovarian cancer (OC), a notably challenging disease characterized by poor responses to both single and combination ICI therapies.
Interestingly, the infiltration of T cells into the OC TME is linked to enhanced progression-free survival (PFS) and overall survival (OS), yet an immunosuppressive TME frequently impedes therapeutic efficacy, suggesting cell activity within localized immune niches can impact antitumor immunity.
This review explores the roles of TLS, their maturity, functionality, identification, and related gene signatures; specific immune cells and cytokines that play a role in TLS formation and antitumor response; and other modifiable elements, including gut microbiota, that may drive improving OC survival by leveraging a TLS-driven antitumor response to bolster immunotherapy outcomes.
论文信息
- 作者
- Varghese A、Hess SM、Chilakapati S、Conejo-Garcia JR、McGray AJR、Zsiros E
- 单位
- Department of Gynecologic Oncology, Roswell Park Comprehensive Cancer Center, Buffalo, NY, United States.United States
- 文献类型
- 综述
- 期刊
- Frontiers in immunology2025