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TIL(肿瘤浸润淋巴细胞)动态变化作为 luminal 型乳腺癌新辅助治疗反应的生物标志物

英文原题:Tumor-Infiltrating lymphocyte dynamics as biomarkers of neoadjuvant treatment response in luminal breast cancer.

PubMed 2026/02/27(内容时间) BMC Cancer Q2 · IF 4.1(JCR 2025)

研究概要

基线TIL水平及化疗引起的TIL下降与HR+/HER2乳腺癌新辅助化疗的病理缓解强烈相关。尽管TIL动态变化可能作为治疗疗效的替代标志物,但其在该亚型中对长期结局的预测价值有限。需要更大规模、设计良好的前瞻性研究来进一步阐明这一关系。

研究思路结论见上方概要

TIL(肿瘤浸润淋巴细胞)(TILs)是乳腺癌中已确立的免疫生物标志物;然而,其在激素受体阳性/HER2阴性(HR+/HER2-)疾病中的临床相关性仍存在争议。特别是,TIL动态变化对病理反应的预测价值及其对生存结局的预后意义在该亚型中尚未明确。

本回顾性研究纳入2017年至2025年间接受新辅助化疗的87例HR+/HER2乳腺癌患者。根据国际TILs工作组建议,在治疗前粗针穿刺活检标本和治疗后手术标本中评估间质TILs。Delta-TIL计算为治疗后与治疗前TIL水平之间的变化。采用非参数检验、Kaplan Meier生存分析和Cox回归模型分析TIL参数与病理完全缓解(pCR)和无进展生存期(PFS)之间的关联。

治疗前TIL中位数为15%,新辅助化疗后显著降至10%(p = 0.003)。达到pCR的患者基线TIL水平显著高于未达到pCR的患者(30% vs. 15%,p = 0.027),且治疗后TIL水平显著更低(0% vs. 10%,p < 0.001)。Delta-TIL与pCR密切相关,达到pCR的患者下降幅度更大(32.6% vs. 3.0%,p < 0.001)。达到pCR的患者PFS显著长于未达到pCR的患者。相比之下,基线TIL、治疗后TIL和delta-TIL均不能独立预测PFS。进展风险主要与病理肿瘤负荷和手术因素相关。

展开英文摘要原文

BACKGROUND: Tumor-infiltrating lymphocytes (TILs) are established immune biomarkers in breast cancer; however, their clinical relevance in hormone receptor positive/HER2-negative (HR+/HER2 ) disease remains controversial. In particular, the predictive value of TIL dynamics for pathological response and their prognostic significance for survival outcomes are not clearly defined in this subtype. METHODS: This retrospective study included 87 patients with HR+/HER2 breast cancer who received neoadjuvant chemotherapy between 2017 and 2025. Stromal TILs were assessed in pre-treatment core biopsy specimens and post-treatment surgical samples according to International TILs Working Group recommendations. Delta-TIL was calculated as the change between post-treatment and pre-treatment TIL levels. Associations between TIL parameters and pathological complete response (pCR) and progression-free survival (PFS) were analyzed using non-parametric tests, Kaplan Meier survival analysis, and Cox regression models. RESULTS: Median pre-treatment TIL was 15%, which significantly decreased to 10% after neoadjuvant chemotherapy (p = 0.003). Patients who achieved pCR had significantly higher baseline TIL levels compared with those without pCR (30% vs. 15%, p = 0.027) and markedly lower post-treatment TIL levels (0% vs. 10%, p < 0.001). Delta-TIL showed a strong association with pCR, with greater reductions observed in patients achieving pCR ( 32.6% vs. 3.0%, p < 0.001). Patients who achieved pCR demonstrated significantly longer PFS compared with those without pCR. In contrast, neither baseline TIL, post-treatment TIL, nor delta-TIL independently predicted PFS. Progression risk was primarily associated with pathological tumor burden and surgical factors. CONCLUSION: Baseline TIL levels and chemotherapy-induced reductions in TILs are strongly associated with pathological response to neoadjuvant chemotherapy in HR+/HER2 breast cancer.Although TIL dynamics may serve as a surrogate marker of treatment efficacy, they have limited value for long-term outcomes in this subtype.Larger, well-designed prospective studies are required to further clarify this relationship.

论文信息

作者
Uguztemur E、Dogan M
第一作者单位
Adiyaman Training and Research Hospital Medical Oncology Department, Adiyaman, Turkey. esmauguztemur@hotmail.com.Turkey
通讯作者单位
Pathology Department, Bursa Yuksek Ihtisas Training and Research Hospital, Bursa, Turkey. mddoganmerve@gmail.com.Turkey
期刊
BMC cancer2026 Feb 27
原文标识
PubMed 41749117 · DOI 10.1186/s12885-026-15795-9