The germinal center-tertiary lymphoid structure after neoadjuvant chemo-immunotherapy for locally advanced lung squamous cell carcinoma can predict the disease progression

作者：Shuang Li, Ping Zhou, Yan Huang, Min Chen, Chan Yang, Lili Jiang · 发表于：Frontiers in Immunology · 年份：2025 · DOI：10.3389/fimmu.2025.1579840 · 被引用次数：3 · 研究领域：Cancer Immunotherapy and Biomarkers、Immunotherapy and Immune Responses、Ferroptosis and cancer prognosis

Background The tertiary lymphoid structures (TLSs) are the anti-tumor immune hubs in the tumor microenvironment. The germinal center (GC) (a marker of maturation) and spatial distribution of TLS may determine the responsiveness of immunotherapy. However, the regulatory mechanism of neoadjuvant chemotherapy (NACT) and combined immunotherapy (NACT-IO) on the dynamic remodeling of TLS has not been elucidated. Methods The NACT-IO group (72 patients), NACT group (50 patients), UT group (50 patients, un-neoadjuvant therapy) were included. Multiple immunofluorescence (mIF) was used to analyze the difference of microenvironment in paired samples (the same case) pre and post neoadjuvant therapy. To further analyze the effect of treatment on the maturity and spatial distribution pattern of TLS (within/outside tumor bed) in postoperative samples, and to establish a quantitative method of TLS based on hot spot area to evaluate its prognostic value. Results Spatial heterogeneity analysis that the density of total TLSs (t-TLSs) and GC-positive TLSs (GC-TLSs) in the tumor bed of NACT ( p <0.01, p <0.01) group and NACT-IO ( p <0.001, p <0.001) group were significantly higher than that outside the tumor bed. Compared with the UT group, NACT and NACT-IO significantly increased the density of t-TLSs ( p <0.01, p <0.001) and GC-TLSs ( p <0.01, p <0.01) in the tumor bed. In addition, there was an inverted U-shaped correlation between GC-TLS ...