间皮素作为癌症免疫治疗的生物标志物和治疗靶点
Mesothelin as Biomarker and Therapeutic Target for Immunotherapy in Cancer.
癌症仍是一个关键的全球健康问题,原因在于发现晚、耐药和高死亡率。
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Predicting response to immunotherapy in gastric cancer via multi-dimensional analyses of the tumour immune microenvironment.
Predicting response to immunotherapy in gastric cancer via multi-dimensional analyses of the tumour immune microenvironment.
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单一生物标志物不足以识别有可能从抗PD-1/PD-L1治疗中获益的胃癌(GC)患者,推测是由于肿瘤微环境的复杂性。肿瘤浸润免疫细胞(TIICs)的预测价值就其密度和空间组织而言尚未明确建立。在此,采用多重免疫组化在80例GC患者中以亚细胞分辨率定量原位生物标志物。为预测免疫治疗反应,我们通过考虑CD4+FoxP3-PD-L1+、CD8+PD-1-LAG3-和CD68+STING+细胞的密度以及CD8+PD-1+LAG3-T细胞的空间组织,建立了一个多维TIIC特征。该TIIC特征能够预测GC患者对抗PD-1/PD-L1免疫治疗的反应以及患者生存。我们的发现表明,多维TIIC特征可能与筛选最有可能从抗PD-1/PD-L1免疫治疗中获益的患者相关。
A single biomarker is not adequate to identify patients with gastric cancer (GC) who have the potential to benefit from anti-PD-1/PD-L1 therapy, presumably owing to the complexity of the tumour microenvironment. The predictive value of tumour-infiltrating immune cells (TIICs) has not been definitively established with regard to their density and spatial organisation.
Here, multiplex immunohistochemistry is used to quantify in situ biomarkers at sub-cellular resolution in 80 patients with GC. To predict the response to immunotherapy, we establish a multi-dimensional TIIC signature by considering the density of CD4 + FoxP3 - PD-L1 + , CD8 + PD-1 - LAG3 - , and CD68 + STING + cells and the spatial organisation of CD8 + PD-1 + LAG3 - T cells. The TIIC signature enables prediction of the response of patients with GC to anti-PD-1/PD-L1 immunotherapy and patient survival.
Our findings demonstrate that a multi-dimensional TIIC signature may be relevant for the selection of patients who could benefit the most from anti-PD-1/PD-L1 immunotherapy.
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