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:Immune Landscape of Epstein-Barr Virus-Associated Gastric Cancer: Analysis From a Western Academic Institution.
Immune Landscape of Epstein-Barr Virus-Associated Gastric Cancer: Analysis From a Western Academic Institution.
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本中心手术切除的 EBVaGC 发生率为 4%。EBVaGC 肿瘤在肿瘤及肿瘤相关间质中均具有升高的 TILs 水平,包括记忆亚型。EBVaGC 中显著的 TIL 存在和上调的 PD-L1 阳性可能预示对免疫治疗药物有良好反应。可能有必要进一步研究胃癌患者的常规 EBV 检测和 TIL 表型,以预测对免疫治疗的反应。
EBV相关胃癌(EBVaGC)可能是免疫治疗潜在获益的有意义生物标志物。需要进一步研究以刻画EBVaGC的免疫景观。我们评估了本机构接受手术治疗的EBVaGC发生频率,并分析了一系列EBVaGC相较于非EBVaGC病例的免疫生物标志物谱和TIL(肿瘤浸润淋巴细胞)表型。
收集了2012年至2020年期间在本机构接受根治性切除术的所有经活检确诊为胃腺癌患者的可用组织样本。采用原位杂交评估EBV状态;采用多重免疫组化评估错配修复状态、程序性死亡配体 1(PD-L1)表达以及TILs的表型特征。
本研究共纳入68例样本。EBVaGC存在于3/68(4%)例患者中。在所有患者中,27/68(40%)例PD-L1表达阳性;3例EBVaGC患者中有2例(67%)表现出PD-L1表达阳性。与非EBVaGC相比,EBV阳性肿瘤在肿瘤和间质中均显示出高5倍至10倍的TILs密度,并且CD8+ T细胞与Tregulatory细胞比值显著升高。与非EBVaGC相比,EBVaGC肿瘤和间质组织中CD8+和CD4+ T细胞的记忆亚型上调。
Available tissue samples from all patients with biopsy-confirmed gastric adenocarcinoma who underwent resection with curative intent from 2012 to 2020 at our institution were collected. In situ hybridization was used to assess EBV status; multiplex immunohistochemistry was performed to assess mismatch repair status, Programmed Death-Ligand 1 (PD-L1) expression, and phenotypic characterization of TILs.
Sixty-eight samples were included in this study. EBVaGC was present in 3/68 (4%) patients. Among all patients, 27/68 (40%) had positive PD-L1 expression; two of three (67%) EBVaGC patients exhibited positive PD-L1 expression. Compared to non-EBVaGC, EBV-positive tumors showed 5-fold to 10-fold higher density of TILs in both tumor and stroma and substantially elevated CD8+ T cell to Tregulatory cell ratio. The memory subtypes of CD8+ and CD4+ T cells were upregulated in EBVaGC tumors and stromal tissue compared to non-EBVaGC.
The incidence of surgically resected EBVaGC at our center was 4%. EBVaGC tumors harbor elevated levels of TILs, including memory subtypes, within both tumor and tumor-related stroma. Robust TIL presence and upregulated PD-L1 positivity in EBVaGC may portend promising responses to immunotherapy agents. Further investigation into routine EBV testing and TIL phenotype of patients with gastric cancer to predict response to immunotherapy may be warranted.
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