基于三级淋巴结构的三阴性乳腺癌免疫治疗相关免疫细胞表型筛选研究-现代医学

基于三级淋巴结构的三阴性乳腺癌免疫治疗相关免疫细胞表型筛选研究

单位：1. 徐州市中心医院乳腺外科, 江苏徐州 221000;
2. 徐州市中心医院肿瘤内科, 江苏徐州 221000

分类号：R737.9

出版年·卷·期（页码）：2026·45·第四期（675-681）

摘要：

目的： 探究三阴性乳腺癌(TNBC)中三级淋巴结构(TLS)免疫细胞表型，筛选免疫治疗相关的潜在生物标志物。方法： 纳入接受新辅助免疫治疗的TNBC患者50例，获取治疗前后含TLS区域肿瘤组织，采用流式细胞术检测免疫细胞亚群，ELISA检测IgG、IgA、IgM水平，CD8⁺T细胞杀伤实验评估细胞毒活性；采用配对t检验或Wilcoxon符号秩检验进行统计分析。结果： 与治疗前比较，免疫治疗后CD8⁺T细胞比例显著升高(P<0.001)；CD4⁺T细胞比例及CD4⁺/CD8⁺比值显著降低(P<0.001)；CXCL13⁺ CD4⁺Tfh细胞、TIM3⁺ PD-1⁺ CD8⁺T细胞、记忆B细胞、浆细胞比例均显著上升(P<0.001)；IgG、IgA、IgM浓度显著升高(P<0.001)；CD8⁺T细胞杀伤效率由27.7%±6.8%提升至61.5%±5.2%(P<0.001)。结论： 免疫治疗可重塑TNBC中TLS免疫微环境，激活TNBC患者含TLS区域肿瘤组织中的细胞免疫及体液免疫应答；CXCL13⁺ CD4⁺Tfh细胞、TIM3⁺ PD-1⁺ CD8⁺T细胞、记忆B细胞的动态变化可反映免疫微环境重塑过程，为理解TLS在免疫治疗中的作用提供实验依据。

Objective: To investigate immune cell phenotypes within tertiary lymphoid structures(TLS) in triple-negative breast cancer(TNBC) and to identify potential biomarkers associated with immunotherapy response. Methods: Fifty patients with TNBC receiving neoadjuvant immunotherapy were enrolled. TLS-containing tumor tissues were collected before and after treatment. Immune cell subsets were analyzed using flow cytometry; serum levels of IgG, IgA, and IgM were quantified by enzyme-linked immunosorbent assay(ELISA); and CD8⁺T-cell cytotoxicity was evaluated using a cytotoxicity killing assay. Statistical analyses were performed using paired t-tests or Wilcoxon signed-rank tests. Results: Compared with pre-treatment levels, the proportion of CD8⁺T cells significantly increased after immunotherapy(P<0.001), whereas the proportion of CD4⁺T cells and the CD4⁺ /CD8⁺ ratio were significantly decreased(both P<0.001). Conversely, the frequencies of CXCL13⁺ CD4⁺T follicular helper(Tfh) cells, TIM3⁺ PD-1⁺ CD8⁺T cells, memory B cells, and plasma cells all increased significantly(P<0.001). IgG, IgA, and IgM also increased significantly(P<0.001). Moreover, the cytotoxic activity of CD8⁺T cells increased from 27.7%±6.8% to 61.5%±5.2%(P<0.001). Conclusion: Immunotherapy effectively remodels the immune microenvironment within TLS in TNBC, activating both cellular and humoral immune responses in TLS-containing tumor tissues. Dynamic changes in CXCL13⁺ CD4⁺Tfh cells, TIM3⁺ PD-1⁺ CD8⁺T cells, and memory B cells may serve as indicators of this remodeling process, supporting the functional role of TLS in immunotherapy.

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