基于 DNA 超分子水凝胶的保护性 NK 细胞储库用于增强三阴性乳腺癌治疗
Protective NK Cell Reservoir Based on DNA Supramolecular Hydrogel for Enhanced Triple-Negative Breast Cancer Therapy.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
免疫浸润、效应 T 细胞富集与功能背景用于预测乳腺癌新辅助化疗病理完全缓解
英文原题：Immune Infiltration, Effector T-Cell Enrichment, and Functional Context for Prediction of Pathologic Complete Response to Neoadjuvant Chemotherapy in Breast Cancer.
查看英文原题
Immune Infiltration, Effector T-Cell Enrichment, and Functional Context for Prediction of Pathologic Complete Response to Neoadjuvant Chemotherapy in Breast Cancer.
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中文摘要
TIL（肿瘤浸润淋巴细胞）（TILs）是乳腺癌新辅助化疗（NACT）后病理完全缓解（pCR）的既定预测因子。然而，TILs主要反映免疫浸润的程度，对免疫功能状态的提示有限。
我们研究了整合免疫浸润（TILs）、效应T细胞存在（CD8）和功能背景（免疫检查点组分）的指标是否能在TILs之外改善对pCR的预测。对166例接受标准NACT治疗的早期乳腺癌患者治疗前肿瘤活检样本进行了基质TILs评估，并检测了CD8、PD-1、LAG-3和TIM-3的mRNA表达。采用单变量和多变量逻辑回归评估与pCR的关联，并构建复合免疫表型以捕捉功能性免疫状态。在单变量分析中，较高的TILs、CD8、PD-1和LAG-3与pCR相关（均p < 0.05），而TIM-3则不相关（p = 0.801）。在多变量模型中，校正检查点标志物后，TILs仍与pCR独立相关，但纳入CD8后该关联减弱，这与TILs和CD8之间强烈的生物学相关性一致，且CD8和检查点标志物均未保留独立显著性。PD-1和LAG-3表达与CD8强相关，与TILs中度相关，表明检查点表达主要反映免疫效应细胞参与的肿瘤微环境。基于CD8/PD-1共表达的复合免疫表型识别出不同的免疫功能状态，其中CD8高/PD-1高肿瘤表现出最高的pCR率。分层建模显示，将免疫变量依次加入临床预测因子后，区分度有适度提升，其中整合 CD8/PD-1 模型在该队列中达到最高区分度（AUC = 0.849），尽管在 TIL 评估之外，提升幅度有限。
总之，免疫浸润、效应 T 细胞的存在以及功能性免疫背景，代表了乳腺癌 NACT 后 pCR 预测的互补维度。然而，TIL 仍是最稳健且临床可行的免疫生物标志物。
展开英文摘要原文
Tumor-infiltrating lymphocytes (TILs) are an established predictor of pathological complete response (pCR) after neoadjuvant chemotherapy (NACT) in breast cancer.
However, TILs primarily reflect the extent of immune infiltration and provide limited insight into immune functional state.
We investigated whether integrating measures of immune infiltration (TILs), effector T-cell presence (CD8), and functional context (immune checkpoint components) may improve prediction of pCR beyond TILs alone. Pretreatment tumor biopsies from 166 patients with early breast cancer treated with standard NACT were assessed for stromal TILs and mRNA expression of CD8, PD-1, LAG-3, and TIM-3. Associations with pCR were evaluated using univariate and multivariable logistic regression, and composite immune phenotypes were constructed to capture functional immune states. In univariate analyses, higher TILs, CD8, PD-1, and LAG-3 were associated with pCR (all p < 0. 05), whereas TIM-3 was not ( p = 0. 801).
In multivariable models, TILs remained independently associated with pCR when adjusted for checkpoint markers, but this association was attenuated when CD8 was included, consistent with the strong biological correlation between TILs and CD8, and neither CD8 nor checkpoint markers retained independent significance. PD-1 and LAG-3 expression strongly correlated with CD8 and moderately correlated with TILs, indicating that checkpoint expression predominantly reflects an immune effector-engaged tumor microenvironment.
Composite immune phenotypes based on CD8/PD-1 co-expression identified distinct immune functional states, with CD8-high/PD-1-high tumors demonstrating the highest pCR rates. Hierarchical modeling showed modest improvements in discrimination with sequential addition of immune variables to clinical predictors, with the integrative CD8/PD-1 model achieving the highest discrimination within the cohort (AUC = 0. 849), although the magnitude of improvement beyond TIL assessment alone was limited.
In conclusion, immune infiltration, effector T-cell presence, and functional immune context represent complementary dimensions for pCR prediction following NACT in breast cancer.
However, TILs remain the most robust and clinically feasible immune biomarker.
论文信息
- 作者
- Demšar A、Geršak K、Gazić B、Blagus T、Goričar K、Jezernik G、Dolžan V、Grašič Kuhar C
- 第一作者单位
- Faculty of Medicine, University of Maribor, Taborska Ulica 8, 2000 Maribor, Slovenia.
- 通讯作者单位
- Faculty of Medicine, University of Ljubljana, Vrazov Trg 2, 1000 Ljubljana, Slovenia.
- 期刊
- International journal of molecular sciences2026 Mar 6
- 原文标识
- PubMed 41828646 · DOI 10.3390/ijms27052431
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