RNF43 p.G659fs 通过 PI3K/AKT/mTOR 信号通路和 HLA-E 上调导致 MSI-high 结直肠癌中 NK 细胞功能障碍
RNF43 p.G659fs leads to natural killer cell dysfunction in MSI-high colorectal cancer through PI3K/AKT/mTOR signaling and HLA-E up-regulation.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
直接 CD32 T 细胞细胞毒性：对乳腺癌预后和治疗的意义
英文原题：Direct CD32 T-cell cytotoxicity: implications for breast cancer prognosis and treatment.
查看英文原题
Direct CD32 T-cell cytotoxicity: implications for breast cancer prognosis and treatment.
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中文摘要
FcγRII（CD32）配体是IgFc片段和五聚素。其他配体是否存在尚不清楚。我们通过将CD32胞外部分与跨膜CD8α融合，并连接至CD28/ζ链胞内部分（CD32-CR），构建了表达人嵌合受体的T细胞。转导后的T细胞在无靶向抗体的情况下，识别了15种受测细胞系中的3种乳腺癌（BC）细胞系和1种结肠癌细胞系。敏感的BC细胞与CD32-CR T细胞结合后，诱导了CD32极化与下调、CD107a释放、相互杀伤以及促炎细胞因子产生，这些效应不受人IgG影响，但可被cetuximab增强。CD32-CR T细胞保护免疫缺陷小鼠免受MDA-MB-468 BC细胞皮下生长的影响。RNAseq分析鉴定出一个42基因指纹，可预测BC细胞敏感性以及晚期BC的良好结局。ICAM1是CD32-CR T细胞介导细胞毒性的主要调控因子。CD32-CR T细胞可能有助于鉴定细胞表面CD32配体和新的具有预后相关性的转录组特征，并开发创新的BC治疗方法。
展开英文摘要原文
The FcγRII (CD32) ligands are IgFc fragments and pentraxins. The existence of additional ligands is unknown.
We engineered T cells with human chimeric receptors resulting from the fusion between CD32 extracellular portion and transmembrane CD8α linked to CD28/ζ chain intracellular moiety (CD32-CR). Transduced T cells recognized three breast cancer (BC) and one colon cancer cell line among 15 tested in the absence of targeting antibodies. Sensitive BC cell conjugation with CD32-CR T cells induced CD32 polarization and down-regulation, CD107a release, mutual elimination, and proinflammatory cytokine production unaffected by human IgGs but enhanced by cetuximab.
CD32-CR T cells protected immunodeficient mice from subcutaneous growth of MDA-MB-468 BC cells. RNAseq analysis identified a 42 gene fingerprint predicting BC cell sensitivity and favorable outcomes in advanced BC. ICAM1 was a major regulator of CD32-CR T cell-mediated cytotoxicity. CD32-CR T cells may help identify cell surface CD32 ligand(s) and novel prognostically relevant transcriptomic signatures and develop innovative BC treatments.
论文信息
- 作者
- Sconocchia G、Lanzilli G、Cesarini V、Silvestris DA、Rezvani K、Arriga R、Caratelli S、Chen K
- 第一作者单位
- Department of Biomedicine Institute of Translational Pharmacology (IFT), National Research Council (CNR), Rome, Italy giuseppe.sconocchia@ift.cnr.it.Italy
- 通讯作者单位
- Department of Internal Medicine, Division of Hematology, Medical University of Graz, Graz, Austria giuseppe.sconocchia@ift.cnr.it.Austria
- 文献类型
- 非美国政府资助研究
- 期刊
- Life science alliance2022 Dec
- 原文标识
- PubMed 36241426 · DOI 10.26508/lsa.202201590
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