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:The Presence of CD11c+ B Cells with Potent Effector Memory Phenotype in Lung Adenocarcinoma Correlates with Overall Patient Survival.
The Presence of CD11c+ B Cells with Potent Effector Memory Phenotype in Lung Adenocarcinoma Correlates with Overall Patient Survival.
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肿瘤浸润B淋巴细胞(TIL-B)日益被视为多种癌症的有利预后标志物,相关机制正在积极研究。本研究将CD79A确立为可靠的B淋巴细胞定量指标,并评估来自癌症基因组图谱(TCGA)的15种不同肿瘤、共8,720份未经治疗患者样本及基因组织表达数据库中的正常组织转录组数据。部分肿瘤的B淋巴细胞浸润与生存相关,但并非所有肿瘤均如此。在肺腺癌(LUAD)中,CD79A水平可强力预测总生存期,而CD8A转录本并无此效应,提示白细胞总体浸润本身不足以解释B细胞的影响。单细胞RNA测序和流式细胞术发现,与正常组织和血液相比,未经治疗LUAD患者的CD11c阳性B细胞相对数量增加。在LUAD中,CD11c阳性TIL-B定位于CD4阳性T细胞附近;体外抗IgG刺激(单独或联合CD40激动剂)可使其扩增并快速分化。刺激还诱导IL-12、IL-21和TNF分泌,这些细胞因子已知可增强抗肿瘤免疫。
总体而言,数据表明CD11c阳性TIL-B可能成为抗癌治疗靶点,和/或潜在的癌症预后生物标志物。
Tumor-infiltrating B lymphocytes (TIL-B) are increasingly recognized as favorable prognostic markers in multiple cancer types, and the mechanisms underlying this are being actively investigated. In this study of TIL-Bs, we identified CD79A as a reliable quantifier of B lymphocytes and evaluated transcriptomic data for 15 distinct tumors using 8,720 samples of treatment na ve patients from The Cancer Genome Atlas and normal tissues from Gene Tissue Expression. B-lymphocyte infiltration correlated with survival for some but not all tumors.
In lung adenocarcinoma (LUAD), CD79A levels were strongly predictive of overall survival, whereas CD8A transcripts were not, indicating that leukocytic infiltration per se does not explain the B cell's impact. Single-cell RNA sequencing and flow cytometry identified increased relative numbers of CD11c+ B cells in patients with treatment-na ve LUAD compared with normal tissue and blood.
In LUAD, CD11c+ TIL-Bs were localized near CD4+ T cells, and in vitro stimulation with anti-IgG with/without CD40 agonist resulted in expansion and rapid differentiation. Stimulation also induced IL12, IL21, and TNF secretion, which are cytokines known to enhance antitumor immunity.
Overall, the data indicate that CD11c+ TIL-Bs are a potential target for anticancer therapeutic approaches and/or a potential prognostic biomarker for cancer prognosis.
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