免疫检查点阻断通过扩增效应 CD8⁺ T 细胞克隆增强淋巴细胞清除性化疗诱导的抗肿瘤免疫
Immune Checkpoint Blockade Augments Lymphodepleting Chemotherapy-Induced Antitumor Immunity by Expanding Effector CD8+ T-cell Clones.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Immune Phenotyping Using Neutrophil-to-Lymphocyte Ratio and Tumor-Infiltrating Lymphocytes Predicts Recurrence in Resected Melanoma.
Immune Phenotyping Using Neutrophil-to-Lymphocyte Ratio and Tumor-Infiltrating Lymphocytes Predicts Recurrence in Resected Melanoma.
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TIL(肿瘤浸润淋巴细胞)和中性粒细胞/淋巴细胞比值(NLR)均与黑色素瘤预后相关,但两者联合的预后价值尚未充分明确。本研究旨在评估将NLR和TIL整合为联合免疫表型,能否改善对已切除皮肤黑色素瘤患者无复发生存期(RFS)的预测。
共纳入203例患者。受试者工作特征分析确定RFS的NLR截点为2.75,分为低值组(<2.75)和高值组(≥2.75)。TIL状态分为存在或缺失。根据NLR-TIL联合特征,患者首先分为三种免疫表型:有利型(NLR低且TIL阳性)、中间型(NLR低且TIL阴性,或NLR高且TIL阳性)及不利型(NLR高且TIL阴性)。二分类分析时,将中间型和不利型合并,并与有利型比较。使用Kaplan-Meier曲线和Cox回归模型评估临床病理因素与RFS的关联。
中位随访时间为56个月。单变量分析中,III期疾病、Breslow厚度较大、有丝分裂率升高以及未接受辅助治疗均与RFS较差相关。此外,与有利组相比,不利免疫表型患者的复发风险显著升高(HR=2.86,95% CI 1.43–5.71;P=0.004)。多变量Cox回归分析显示,不利免疫表型和III期疾病均可独立预测RFS(分别为HR=2.25,95% CI 1.11–4.54;P=0.024,以及HR=2.13,95% CI 1.03–4.43;P=0.041)。
联合评估NLR和TIL所反映的全身炎症及肿瘤局部免疫应答,有望为已切除皮肤黑色素瘤提供有意义的预后分层。
Background and Objectives: Tumor-infiltrating lymphocytes (TIL) and the neutrophil-to-lymphocyte ratio (NLR) are each associated with prognosis in melanoma, yet their combined prognostic value remains insufficiently defined.
We aimed to assess whether integrating NLR and TILs into a combined immune phenotype improves prediction of recurrence-free survival (RFS) in patients with resected cutaneous melanoma. Materials and Methods: A total of 203 patients were included. Receiver operating characteristic analysis identified an NLR cut-off of 2. 75 for RFS, defining low (<2. 75) and high ( 2. 75) groups. TIL status was dichotomized as present or absent. According to the combined NLR-TIL profile, patients were initially categorized into three immune phenotypes: favorable (low NLR and TIL-positive), intermediate (low NLR and TIL-negative or high NLR and TIL-positive), and unfavorable (high NLR and TIL-negative).
For the dichotomized analysis, the intermediate and unfavorable phenotypes were combined and compared with the favorable phenotype. Associations of clinicopathological factors with RFS were evaluated using Kaplan-Meier curves and Cox regression models. Results: The median follow-up was 56 months. In the univariate analysis, stage III disease, greater Breslow thickness, increased mitotic rate, and absence of adjuvant therapy were associated with worse RFS.
In addition, patients with an unfavorable immune phenotype had a markedly increased risk of recurrence compared with those in the favorable group (HR 2. 86, 95% CI 1. 43-5. 71; p = 0. 004). In multivariate Cox regression analysis, both the unfavorable immune phenotype and stage III disease independently predicted RFS (HR 2.
25, 95% CI 1. 11-4. 54; p = 0. 024 and HR 2. 13, 95% CI 1. 03-4. 43; p = 0. 041, respectively). Conclusions: Combined assessment of systemic inflammation and tumor-local immune response using NLR and TILs may provide meaningful prognostic stratification in resected cutaneous melanoma.
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