一种用于克服非小细胞肺癌治疗中抗原异质性的多靶向 CAR-T 细胞平台
A Multi-Targeting Chimeric Antigen Receptor-T Cell Platform to Overcome Antigen Heterogeneity in the Treatment of Non-Small Cell Lung Cancer.
这些发现支持采用多靶点CAR-T 策略来应对NSCLC及可能其他实体瘤中的抗原异质性。
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Prognostic Impact of the Immune-Cell Infiltrate in N1-Positive Non-Small-Cell Lung Cancer.
Prognostic Impact of the Immune-Cell Infiltrate in N1-Positive Non-Small-Cell Lung Cancer.
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对特定瘤内免疫细胞的评估可作为 pN1 NSCLC 的预后预测指标。然而,观察到的差异与腺癌或鳞状细胞癌组织学类型相关。对免疫细胞浸润的前瞻性评估及其预后相关性的进一步阐明,可能有助于为即将开展的围手术期免疫治疗筛选患者。
肿瘤免疫微环境在非小细胞肺癌(NSCLC)的发生发展中起着至关重要的作用,并可能影响个体预后。我们分析了肺癌根治性手术后免疫细胞浸润的预测作用。
对174例pN1 NSCLC并接受辅助化疗患者的肿瘤免疫细胞浸润情况采用免疫荧光染色进行了特征分析。特定免疫细胞在肿瘤中心(TU)、浸润前沿(IF)和正常组织(NORM)中的密度与分布与临床参数及生存数据进行了相关性分析。
所有患者的肿瘤特异性生存(TSS)5年时为69.9%。TIL(肿瘤浸润淋巴细胞)密度在TU和IF中高于NORM。TU中高TIL密度(低 vs. 高:62.0% vs. 86.7%;p = .011)以及TU和IF中存在细胞毒性T淋巴细胞(CTL)与TSS改善相关(阳性 vs. 阴性:90.6% vs. 64.7%,p = .024)。高TIL密度与程序性死亡配体 1表达水平50%相关(p < .001)。多因素分析确定TU中TIL积聚(p = .016)和低Treg密度(p = .003)为鳞状细胞癌的负向预后预测因素(p = .025),而M1样肿瘤相关巨噬细胞(p = .019)和高程序性死亡配体 1状态(p = .038)与腺癌中更好的生存相关。
The tumoral immune-cell infiltrate from 174 patients with pN1 NSCLC and adjuvant chemotherapy was characterized using immunofluorescence staining. The density and distribution of specific immune cells in tumor center (TU), invasive front (IF) and normal tissue (NORM) were correlated with clinical parameters and survival data.
Tumor specific survival (TSS) of all patients was 69.9% at 5 years. The density of tumor infiltrating lymphocytes (TIL) was higher in TU and IF than in NORM. High TIL density in TU (low vs. high: 62.0% vs. 86.7%; p = .011) and the presence of cytotoxic T-Lymphocytes (CTLs) in TU and IF were associated with improved TSS (positive vs. negative: 90.6% vs. 64.7% p = .024). High TIL-density correlated with programmed death-ligand 1 expression levels 50% (p < .001). Multivariate analysis identified accumulation of TIL (p = .016) and low Treg density (p = .003) in TU as negative prognostic predictors in squamous cell carcinoma (p = .025), whereas M1-like tumor- associated macrophages (p = .019) and high programmed death-ligand 1 status (p = .038) were associated with better survival in adenocarcinoma.
The assessment of specific intratumoral immune cells may serve as a prognostic predictor in pN1 NSCLC. However differences were observed related to adenocarcinoma or squamous cell carcinoma histology. Prospective assessment of the immune-cell infiltrate and further clarification of its prognostic relevance could assist patient selection for upcoming perioperative immunotherapies.
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