State Key Laboratory for Oncogenes and Related Genes; Key Laboratory of Gastroenterology & Hepatology, Ministry of Health; Division of Gastroenterology and Hepatology; Shanghai Institute of Digestive Disease; Renji Hospital, Shanghai Jiao Tong University School of Medicine, 145 Middle Shandong Road, Shanghai, 200001, China.
Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, 510080, China.
Mol Cancer. 2022 Jan 2;21(1):2. doi: 10.1186/s12943-021-01462-z.
In recent years, the application of functional genetic immuno-oncology screens has showcased the striking ability to identify potential regulators engaged in tumor-immune interactions. Although these screens have yielded substantial data, few studies have attempted to systematically aggregate and analyze them.
In this study, a comprehensive data collection of tumor immunity-associated functional screens was performed. Large-scale genomic data sets were exploited to conduct integrative analyses.
We identified 105 regulator genes that could mediate resistance or sensitivity to immune cell-induced tumor elimination. Further analysis identified MON2 as a novel immune-oncology target with considerable therapeutic potential. In addition, based on the 105 genes, a signature named CTIS (CRISPR screening-based tumor-intrinsic immune score) for predicting response to immune checkpoint blockade (ICB) and several immunomodulatory agents with the potential to augment the efficacy of ICB were also determined.
Overall, our findings provide insights into immune oncology and open up novel opportunities for improving the efficacy of current immunotherapy agents.
近年来，功能遗传免疫肿瘤学筛选的应用展示了识别参与肿瘤免疫相互作用的潜在调节剂的惊人能力。尽管这些筛选产生了大量的数据，但很少有研究试图对其进行系统地汇总和分析。
本研究对肿瘤免疫相关的功能筛选进行了全面的数据收集。利用大规模基因组数据集进行综合分析。
我们确定了 105 个能够调节免疫细胞诱导的肿瘤消除的抵抗或敏感性的调节基因。进一步的分析确定了 MON2 作为一个具有相当治疗潜力的新型免疫肿瘤学靶标。此外，基于这 105 个基因，我们确定了一个名为 CTIS（基于 CRISPR 筛选的肿瘤内在免疫评分）的特征，用于预测对免疫检查点阻断（ICB）和几种具有增强 ICB 疗效潜力的免疫调节剂的反应。
总的来说，我们的发现为免疫肿瘤学提供了新的见解，并为改善当前免疫治疗药物的疗效开辟了新的机会。
