Clinical and Immunological Implications of Frameshift Mutations in Lung Cancer
Clinical and Immunological Implications of Frameshift Mutations in Lung Cancer
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DOI：
10.1016/j.jtho.2019.06.016
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发表时间：
2019-10-01
影响因子：
20.4
通讯作者：
Park, Wungki
中科院分区：
文献类型：
--
作者：
Chae, Young Kwang;Viveiros, Pedro;Park, Wungki
简介：目前，程序性死亡配体1是预测NSCLC中对免疫检查点抑制剂（ICI）反应的最常用生物标志物。由于它的一些局限性，人们不断寻找更精确和可靠的标记。通过插入或缺失的移码突变（fsindels）被认为诱导更具免疫原性的肿瘤特异性新抗原，从而赋予对ICI的更好应答。已在黑色素瘤和肾细胞癌中研究了fsindel与ICI反应的正相关性。我们研究了fsindels在ICIS.Methods治疗的NSCLC患者的临床结局和免疫景观中的意义：我们利用癌症基因组图谱数据集分析肿瘤突变负荷，新抗原负荷和免疫景观与fsindel状态的关系。此外，我们还利用122例接受ICI治疗的患者的临床数据，评估了fsindel对疾病缓解率和生存结局的影响。结果：fsindel负荷与肿瘤突变负荷和活化的CD 4/CD 8 T细胞浸润之间呈正相关。fsindels的存在也与接受ICI治疗的患者的无进展生存期显著延长相关（中位数6.2 vs 2.7个月[p = 0.01]）。此外，在总的反应率（26%与12% [p = 0.04]）和疾病控制率（68%与48% [p = 0.02]）的显着差异观察fsindels.Conclusion患者：我们的研究结果表明，fsindels可能有预测作用ICI反应在NSCLC。(C)2019年国际肺癌研究协会。爱思唯尔公司出版All rights reserved.
Introduction: Presently, programmed death ligand 1 is the most commonly used biomarker to predict response to immune checkpoint inhibitors (ICIs) in NSCLC. Owing to its several limitations, there is continuous search for more precise and reliable markers. Frameshift mutations by insertion or deletion (fsindels) are suggested to induce more immunogenic tumor-specific neoantigens, conferring better response to ICIs. Positive correlation of fsindels with ICI response has been studied in melanoma and renal cell carcinoma. We investigated the implication of fsindels in the clinical outcomes and immune landscape of patients with NSCLC treated with ICIs.Methods: We utilized The Cancer Genome Atlas data set to analyze tumor mutational burden, neoantigen burden, and immune landscape in relation to fsindel status. In addition, utilizing the clinical data from 122 patients treated with ICIs, we evaluated the influence of fsindels on disease response rates and survival outcomes.Results: A positive correlation between fsindel burden and tumor mutational burden and activated CD4/CD8 T-cell infiltration was shown. Presence of fsindels was also associated with significant prolongation of progression-free survival in patients treated with ICIs (median 6.2 versus 2.7 months [p = 0.01]). In addition, significant differences in the overall response rates (26% versus 12% [p = 0.04]) and disease control rates (68% versus 48% [p = 0.02]) were observed in patients with fsindels.Conclusion: Our findings suggest that fsindels may have a predictive role for ICI response in NSCLC. (C) 2019 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.