Pritzker School of Medicine, The University of Chicago, Chicago, IL, USA.
Department of Radiation and Cellular Oncology, The University of Chicago, Chicago, IL, USA.
Sci Rep. 2024 Aug 21;14(1):19375. doi: 10.1038/s41598-024-66062-5.
Recent studies have linked elevated tumor aneuploidy to anti-tumor immune suppression and adverse survival following immunotherapy. Herein, we provide supportive evidence for tumor aneuploidy as a biomarker of response to immunotherapy in patients with non-small cell lung cancer (NSCLC). We identify a dose-response relationship between aneuploidy score and patient outcomes. In two independent NSCLC cohorts (n = 659 patients), we demonstrate a novel association between elevated aneuploidy and non-smoking-associated oncogenic driver mutations. Lastly, we report enrichment of TERT amplification and immune-suppressive phenotypes of highly aneuploid NSCLC. Taken together, our findings emphasize a potentially critical role for tumor aneuploidy in guiding immunotherapy treatment strategies.
最近的研究将肿瘤非整倍性与抗肿瘤免疫抑制和免疫治疗后的不良生存联系起来。在此，我们为肿瘤非整倍性作为非小细胞肺癌（NSCLC）患者免疫治疗反应的生物标志物提供了支持性证据。我们确定了非整倍性评分与患者结局之间的剂量反应关系。在两个独立的 NSCLC 队列（n=659 名患者）中，我们证明了非整倍性升高与非吸烟相关的致癌驱动基因突变之间存在新的关联。最后，我们报告了 TERT 扩增和高度非整倍体 NSCLC 的免疫抑制表型富集。总之，我们的发现强调了肿瘤非整倍性在指导免疫治疗策略方面的潜在关键作用。
