三级淋巴结构异质性在三阴性乳腺癌新辅助治疗中的预测作用及免疫微环境特征的研究现状与展望

doi:10.19401/j.cnki.1007-3639.2025.02.008

摘要/Abstract

摘要：

三阴性乳腺癌（triple-negative breast cancer，TNBC）是一种高度侵袭性且预后不良的乳腺癌亚型，三级淋巴结构（tertiary lymphoid structure，TLS）是肿瘤微环境中的免疫活性区域，由树突状细胞、B细胞、T细胞等免疫细胞组成，能够调节肿瘤免疫反应。TLS在TNBC中的异质性特征，如密度、结构成熟度和分子表达模式，影响着肿瘤免疫微环境，进而影响治疗反应和临床表现。研究表明，TLS的密度和成熟度与TNBC患者的病理学完全缓解（pathological complete response，pCR）呈正相关，TLS通过增强肿瘤浸润免疫细胞的数量，改善抗肿瘤免疫反应，增加TNBC对化疗和免疫治疗的敏感性。最新研究发现，成熟的TLS与有效的免疫反应相关，成为预测治疗反应的重要标志物。将TLS与免疫检查点抑制剂联合应用，展现出良好的治疗前景。此外，有研究表明，促进TLS的形成或增强其功能，可以提高抗肿瘤免疫效应，改善TNBC患者的治疗效果。通过靶向TLS，能够减少免疫逃逸，提高免疫治疗的敏感性。然而，TLS在临床应用中仍面临挑战，尤其是其异质性对治疗反应的影响。TLS的评估方法尚未标准化，缺乏统一的标准和诊断体系，限制了其广泛应用。未来的研究应着重解决这些问题，开发标准化评估工具，并进一步探讨TLS在免疫逃逸、免疫耐药机制中的作用。本综述总结和分析TLS在TNBC中的研究进展，旨在为确立TNBC患者个体化免疫治疗策略提供新的思路。

关键词: 三级淋巴结构, 三阴性乳腺癌, 新辅助治疗, 免疫微环境

Abstract:

Triple-negative breast cancer (TNBC) is a highly aggressive and prognostically unfavorable subtype. Tertiary lymphoid structure (TLS) within the tumor microenvironment, comprising dendritic cells, B cells, T cells, and other immune cells, modulate the tumor immune response. The heterogeneity of TLS in TNBC, such as density, structural maturity, and molecular expression patterns, affects the tumor immune microenvironment and, consequently, treatment responses and clinical outcomes. Studies indicate a positive correlation between the density and maturity of TLS and the pathological complete response (pCR) of TNBC patients, with TLS enhancing the quantity of tumor-infiltrating immune cells and improving anti-tumor immune responses, thereby increasing sensitivity to chemotherapy and immunotherapy. Recent research has found that mature TLS are associated with effective immune responses, becoming significant predictors of treatment response. The combination of TLS with immune checkpoint inhibitors has shown promising prospects. Research demonstrates that promoting the formation or enhancing the functionality of TLS can improve anti-tumor immune effects and enhance treatment outcomes for TNBC patients. Targeting TLS may reduce immune evasion and increase the sensitivity to immunotherapy. However, clinical application of TLS still faces challenges, particularly the impact of their heterogeneity on treatment response. Current assessment methods for TLS are not standardized, lacking a uniform standard and diagnostic system, which limits their widespread application. Future research should focus on resolving these issues by developing standardized assessment tools and further exploring the role of TLS in immune escape and resistance mechanisms. This review aimed to summarize and analyze the existing research progress on TLS in TNBC, in order to provide new ideas for the development of personalized immunotherapy strategies.

Key words: Tertiary lymphoid structures, Triple-negative breast cancer, Neoadjuvant therapy, Immune microenvironment

中图分类号:

R737.9

王青, 俞育帅, 王晨曦, 姜子荣, 李佳璐, 唐诗聪, 宋传贵. 三级淋巴结构异质性在三阴性乳腺癌新辅助治疗中的预测作用及免疫微环境特征的研究现状与展望[J]. 中国癌症杂志, 2025, 35(2): 213-218.

WANG Qing, YU Yushuai, WANG Chenxi, JIANG Zirong, LI Jialu, TANG Shicong, SONG Chuangui. Current status and prospects of tertiary lymphoid structure heterogeneity in predicting response to neoadjuvant therapy and characterizing immune microenvironment in triple-negative breast cancer[J]. China Oncology, 2025, 35(2): 213-218.

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