Fang Qin, Chen Shuru, Chen Xiaoyue, Zou Wei, Chen Di, Huang Yukang, Wu Chucheng
Huizhou Central People's Hospital, Huizhou, China.
Front Oncol. 2025 Jan 24;15:1480461. doi: 10.3389/fonc.2025.1480461. eCollection 2025.
Although tertiary lymphoid structures (TLS) play crucial roles in the anti-tumor immune response and are associated with favorable prognoses in many solid tumors, the precise mechanisms by which TLSs enhance anti-tumor immunity remain poorly understood. The current study aimed to explore the relationship between the maturity of tertiary lymphoid structures and their key immune cells in combating breast cancer.
In this study, we utilized immunofluorescence and H&E staining to detect tumor-resident memory T cells (Trm) and assess the maturity of TLS, analyzing their distribution and proportion in an annotated cohort of 95 breast cancer patients.
The presence of tumor-associated TLSs was correlated with an improved prognosis in patients with breast cancer. The proportion of CD8+CD103+ resident memory T cells and natural killer (NK) cells within the TLSs was significantly higher than that in areas outside of these structures. Additionally, the proportions of CD103+ CD8+ Trm cells and NK cells were significantly increased with the gradual maturation of TLS. Furthermore, the secretion function of effector molecules by CD8+ CD103+ Trm cells and NK cells within TLSs was significantly enhanced, indicating a strong correlation between the effector function of CD103+ CD8+ Trm and NK cells and the maturity of TLSs.
Our study identifies potential additional prognostic information for the clinical prognosis of breast cancer patients, underscoring the prognostic significance of immune cells within TLS, with a particular focus on CD103+ CD8+ Trm cells and NK cells.
尽管三级淋巴结构(TLS)在抗肿瘤免疫反应中发挥关键作用,且与许多实体瘤的良好预后相关,但TLS增强抗肿瘤免疫的精确机制仍知之甚少。本研究旨在探讨三级淋巴结构的成熟度与其在对抗乳腺癌中的关键免疫细胞之间的关系。
在本研究中,我们利用免疫荧光和苏木精-伊红染色来检测肿瘤驻留记忆T细胞(Trm)并评估TLS的成熟度,分析其在95例乳腺癌患者注释队列中的分布和比例。
肿瘤相关TLS的存在与乳腺癌患者预后改善相关。TLS内CD8+CD103+驻留记忆T细胞和自然杀伤(NK)细胞的比例显著高于这些结构外的区域。此外,随着TLS逐渐成熟,CD103+CD8+Trm细胞和NK细胞的比例显著增加。此外,TLS内CD8+CD103+Trm细胞和NK细胞的效应分子分泌功能显著增强,表明CD103+CD8+Trm和NK细胞的效应功能与TLS的成熟度之间存在强烈相关性。
我们的研究为乳腺癌患者的临床预后确定了潜在的额外预后信息,强调了TLS内免疫细胞的预后意义,尤其关注CD103+CD8+Trm细胞和NK细胞。