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
非小细胞肺癌中 HLA-I 类表达的缺失：与预后及无氧代谢的关联
英文原题：Loss of HLA-class-I expression in non-small-cell lung cancer: Association with prognosis and anaerobic metabolism.
查看英文原题
Loss of HLA-class-I expression in non-small-cell lung cancer: Association with prognosis and anaerobic metabolism.
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中文摘要
肿瘤免疫编辑常导致HLA-I类分子（HLA）表达缺失和免疫监视受损。我们研究了一系列可手术的非小细胞肺癌（NSCLC）中HLA的表达。完全缺失和广泛表达缺失分别见于41.5%和23.4%的病例。低CD8+和FOXP3+TIL密度与HLA缺失显著相关（分别为p < 0.05和p = 0.003）。高PD-L1表达与HLA持续表达相关。HLA表达缺失与LDH5过表达显著相关（p = 0.01），与HIF1的相关性处于边缘水平。细胞系实验证实，缺氧和酸性环境下调HLA的表达。还注意到HLA与Beclin-1表达之间存在直接关联（p = 0.01）。HLA表达缺失与较差的生存相关（p < 0.01），且独立于分期。结论是，HLA-I类分子缺失在NSCLC中常见，并与微环境缺氧和酸性直接相关。
展开英文摘要原文
Cancer immuno-editing frequently leads to loss of HLA-class-I molecule (HLA) expression and impaired immune surveillance.
We investigated the expression of HLAs in a series of operable non-small-cell lung carcinomas (NSCLCs). Complete loss and extensive loss of expression was noted in 41. 5% and 23. 4% of cases, respectively. Low CD8 + and FOXP3 + TIL-density was significantly associated with loss of HLAs (p < 0. 05 and p = 0. 003, respectively). High PD-L1 expression was linked with sustained expression of HLAs. A significant association of loss of HLA-expression with overexpression of LDH5 (p = 0.
01) and marginally with HIF1 was recorded. Cell line experiments confirmed that hypoxia and acidity down-regulate the expression of HLAs. A direct association between HLAs and Beclin-1 expression was also noted (p = 0. 01). Loss of HLA-expression was linked with poorer survival (p < 0. 01), independent of stage. It is concluded that loss of HLA-class-I molecules is frequent in NSCLC and directly linked to micro-environmental hypoxia and acidity.
论文信息
- 作者
- Koukourakis IM、Giatromanolaki A、Mitrakas A、Koukourakis MI
- 第一作者单位
- 1(st) Department of Radiology, Radiotherapy Unit, Aretaieion University Hospital, National and Kapodistrian University of Athens, Athens, Greece.Greece
- 通讯作者单位
- Department of Radiotherapy / Oncology, University Hospital of Alexandroupolis, Democritus University of Thrace, Alexandroupolis, Greece. Electronic address: targ@her.forthnet.gr.Greece
- 文献类型
- 非美国政府资助研究
- 期刊
- Cellular immunology2022 Mar
- 原文标识
- PubMed 35183853 · DOI 10.1016/j.cellimm.2022.104495