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
英文原题:The Thermal Dose of Photothermal Therapy Generates Differential Immunogenicity in Human Neuroblastoma Cells.
The Thermal Dose of Photothermal Therapy Generates Differential Immunogenicity in Human Neuroblastoma Cells.
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光热疗法(PTT)是一种有效的肿瘤清除方法,已成功与免疫治疗联合。然而,除了细胞毒作用外,人们对PTT热剂量如何影响治疗后肿瘤细胞的免疫原性知之甚少。
因此,我们采用普鲁士蓝纳米颗粒光热疗法(PBNP-PTT)给予一系列热剂量,并在两种人神经母细胞瘤细胞系中评估其对肿瘤细胞死亡及相关免疫原性指标的影响:SH-SY5Y(MYCN未扩增)和LAN-1(MYCN扩增)。体外结果显示,PBNP-PTT对两种肿瘤细胞系均产生热剂量依赖性的肿瘤细胞杀伤和免疫原性细胞死亡(ICD)。
然而,在SH-SY5Y细胞中,热剂量对ICD以及共刺激分子、免疫检查点分子、主要组织相容性复合体、NK细胞激活配体和神经母细胞瘤相关抗原表达的影响,显著强于LAN-1细胞;这与LAN-1细胞的高危表型一致。在体外功能性共培养研究中,相同热剂量下,T细胞对SH-SY5Y细胞的细胞毒性显著高于对LAN-1细胞的细胞毒性。这项初步报告提示,研究PTT时应超越仅关注肿瘤清除的传统视角,转而考虑热剂量对免疫原性的影响,以促进PTT在癌症免疫治疗中的成功。
Photothermal therapy (PTT) is an effective method for tumor eradication and has been successfully combined with immunotherapy.
However, besides its cytotoxic effects, little is known about the effect of the PTT thermal dose on the immunogenicity of treated tumor cells.
Therefore, we administered a range of thermal doses using Prussian blue nanoparticle-based photothermal therapy (PBNP-PTT) and assessed their effects on tumor cell death and concomitant immunogenicity correlates in two human neuroblastoma cell lines: SH-SY5Y ( MYCN -non-amplified) and LAN-1 ( MYCN -amplified). PBNP-PTT generated thermal dose-dependent tumor cell killing and immunogenic cell death (ICD) in both tumor lines in vitro.
However, the effect of the thermal dose on ICD and the expression of costimulatory molecules, immune checkpoint molecules, major histocompatibility complexes, an NK cell-activating ligand, and a neuroblastoma-associated antigen were significantly more pronounced in SH-SY5Y cells compared with LAN-1 cells, consistent with the high-risk phenotype of LAN-1 cells.
In functional co-culture studies in vitro, T cells exhibited significantly higher cytotoxicity toward SH-SY5Y cells relative to LAN-1 cells at equivalent thermal doses. This preliminary report suggests the importance of moving past the traditional focus of using PTT solely for tumor eradication to one that considers the immunogenic effects of PTT thermal dose to facilitate its success in cancer immunotherapy.
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