Heterogeneity in tertiary lymphoid structures predicts distinct prognosis and immune microenvironment characterizations of clear cell renal cell carcinoma

作者：Wenhao Xu, Jiahe Lu, Wangrui Liu, Aihetaimujiang Anwaier, Yuhao Wu, Xi Tian, Jiaqi Su, Yuanyuan Qu, Jianfeng Yang, Hailiang Zhang, Dingwei Ye · 发表于：Journal for ImmunoTherapy of Cancer · 年份：2023 · DOI：10.1136/jitc-2023-006667 · 被引用次数：99 · 研究领域：Cancer Immunotherapy and Biomarkers、IL-33, ST2, and ILC Pathways、Immunotherapy and Immune Responses

Background Tertiary lymphoid structures (TLS) are organized aggregates of immune cells that develop postnatally in non-lymphoid tissues and are associated with pathological conditions. TLS typically comprise B-cell follicles containing and are encompassed by T- cell zones and dendritic cells. The prognostic and predictive value of TLS in the tumor microenvironment (TME) as potential mediators of antitumor immunity have gained interest. However, the precise relationship between localization and maturation of TLS and the clinical outcome of their presence in clear cell renal cell carcinoma (ccRCC) is yet to be elucidated. Methods Immunohistochemistry and multispectral fluorescence were used to evaluate the TLS heterogeneity along with TME cell-infiltrating characterizations. A thorough investigation of the prognostic implications of the TLS heterogeneity in 395 patients with ccRCC from two independent cohorts was conducted. Associations between TLS heterogeneity and immunologic activity were assessed by quantifying the immune cell infiltration. Results Infiltrated TLS were identified in 34.2% of the ccRCC samples (N=395). These TLS were found to be tumor-proximal, tumor-distal, or both in 37.8%, 74.1%, and 11.9% of the TLS-positive cases, respectively. A higher proportion of early TLS was found in tumor-distal TLS (p=0.016), while tumor-proximal TLS primarily comprised secondary follicle-like structures (p=0.004). In the main study cohort (Fudan University Shanghai Cancer Cente...