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
英文原题:Are [18F]FDG PET/CT imaging and cell blood count-derived biomarkers robust non-invasive surrogates for tumor-infiltrating lymphocytes in early-stage breast cancer?
Are [18F]FDG PET/CT imaging and cell blood count-derived biomarkers robust non-invasive surrogates for tumor-infiltrating lymphocytes in early-stage breast cancer?
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在本研究中,[18F]FDG PET/CT 与常规 CBC 衍生的生物标志物均不能可靠预测早期 BC 的 TILs 水平。
TIL(肿瘤浸润淋巴细胞)是与早期乳腺癌(BC)预后和治疗应答相关的重要免疫生物标志物,在三阴性亚型中尤为如此。本研究采用机器学习模型,评估 [¹⁸F]FDG PET/CT 成像和常规血细胞计数(CBC)衍生生物标志物能否作为 TIL 的无创替代指标。
回顾性分析 358 例经活检证实的早期浸润性 BC 患者,这些患者均接受了治疗前 [¹⁸F]FDG PET/CT。提取原发肿瘤、淋巴结及淋巴器官(脾脏和骨髓)的 PET 衍生标志物。CBC 衍生标志物包括中性粒细胞/淋巴细胞比值(NLR)和血小板/淋巴细胞比值(PLR)。通过组织学评估 TIL,并分为低(0–10%)、中(11–59%)和高(≥60%)水平。采用 Spearman 秩相关系数评估相关性,并使用多种机器学习算法建立分类和回归模型。
肿瘤 SUVmax 和 SUVmean 与 TIL 水平的相关性最高(ρ 分别为 0.29 和 0.30,两者均 p < 0.001),但 TIL 与 PET 或 CBC 衍生标志物总体关联较弱。CBC 衍生指标均未显示显著相关性或判别能力。机器学习模型无法以满意准确度预测 TIL 水平(最高平衡准确率 = 0.66)。淋巴器官指标(SLR、BLR)和 CBC 参数未显著提高预测价值。讨论:在本研究中,[¹⁸F]FDG PET/CT 和常规 CBC 衍生指标均不能可靠预测早期 BC 的 TIL 水平;但这一结果是在可能存在扫描仪相关差异且 PET 指标范围有限的情况下得出的。未来模型应纳入免疫 PET 等更具针对性的成像方法,以更特异地无创评估免疫浸润并改善个体化治疗策略。
Tumor-infiltrating lymphocytes (TILs) are key immune biomarkers associated with prognosis and treatment response in early-stage breast cancer (BC), particularly in the triple-negative subtype. This study aimed to evaluate whether [18F]FDG PET/CT imaging and routine cell blood count (CBC)-derived biomarkers can serve as non-invasive surrogates for TILs, using machine-learning models. MATERIAL AND METHODS: We retrospectively analyzed 358 patients with biopsy-proven early-stage invasive BC who underwent pre-treatment [18F]FDG PET/CT imaging. PET-derived biomarkers were extracted from the primary tumor, lymph nodes, and lymphoid organs (spleen and bone marrow). CBC-derived biomarkers included neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR). TILs were assessed histologically and categorized as low (0-10%), intermediate (11-59%), or high ( 60%). Correlations were assessed using Spearman's rank coefficient, and classification and regression models were built using several machine-learning algorithms.
Tumor SUVmax and tumor SUVmean showed the highest correlation with TIL levels ( = 0.29 and 0.30 respectively, p < 0.001 for both), but overall associations between TILs and PET or CBC-derived biomarkers were weak. No CBC-derived biomarker showed significant correlation or discriminative performance. Machine-learning models failed to predict TIL levels with satisfactory accuracy (maximum balanced accuracy = 0.66). Lymphoid organ metrics (SLR, BLR) and CBC-derived parameters did not significantly enhance predictive value. DISCUSSION: In this study, neither [18F]FDG PET/CT nor routine CBC-derived biomarkers reliably predict TILs levels in early-stage BC. This observation was made in presence of potential scanner-related variability and for a restricted set of usual PET metrics. Future models should incorporate more targeted imaging approaches, such as immunoPET, to non-invasively assess immune infiltration with higher specificity and improve personalized treatment strategies.
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