Jiang Jinling, Wu Lihong, Yuan Fei, Ji Jun, Lin Xiaojing, Yang Wanning, Wu Junwei, Shi Min, Yang Hui, Ma Yanna, Song Xue, Zhu Zhenggang, Zhang Henghui, Zhang Jun
Department of Oncology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
Genecast Precision Medicine Technology Institute, Beijing, China.
Cancer Med. 2020 Apr;9(7):2299-2308. doi: 10.1002/cam4.2905. Epub 2020 Feb 4.
Brain metastases are one of the most common intracranial neoplasms. Increasing evidence have indicated that systemic immunotherapy may provide long-term benefits for brain metastases. Herein, we presented the results of an immune oncology panel RNA sequencing platform for patients with brain metastases from different primary sites.
We investigated 25 samples of human brain metastases from lung cancer (n = 12), breast cancer (n = 6), and colorectal cancer (n = 7). Besides, 13 paired samples of adjacent noncancerous brain tissue (10 from patients with lung cancer and 3 from patients with breast cancer) were collected as controls. By comparing the brain metastases and paired samples of adjacent noncancerous brain tissue from 13 patients, we detected three upregulated and six downregulated genes, representing the malignant properties of cancer cells and increased immune infiltration in the microenvironment. Next, we profiled the immune-related genes in brain metastases from three primary cancer types.
A group of genes were significantly overexpressed in the microenvironment of brain metastases from lung cancer, covering the checkpoint pathways, lymphocyte infiltration, and TCR-coexpression. Especially, immune checkpoint molecules, PD-L1, PD-L2, and IDO1 were expressed at higher levels in brain metastases from lung cancer than those from the other two cancer types.
This study presents an immune landscape of brain metastases from different cancer types. With high RNA expression levels of PD-1/PD-L1 axis and immune infiltration in brain metastases, it would be worthwhile to explore the efficacy of immune checkpoint blockade for lung cancer patients with intracranial metastases.
脑转移瘤是最常见的颅内肿瘤之一。越来越多的证据表明，全身免疫治疗可能为脑转移瘤带来长期益处。在此，我们展示了一个免疫肿瘤学基因panel RNA测序平台针对来自不同原发部位的脑转移瘤患者的研究结果。
我们研究了25例人脑转移瘤样本，其中肺癌脑转移瘤12例，乳腺癌脑转移瘤6例，结直肠癌脑转移瘤7例。此外，收集了13对相邻非癌脑组织样本（10例来自肺癌患者，3例来自乳腺癌患者）作为对照。通过比较13例患者的脑转移瘤样本和配对的相邻非癌脑组织样本，我们检测到3个上调基因和6个下调基因，这些基因代表了癌细胞的恶性特征以及微环境中免疫浸润的增加。接下来，我们分析了来自三种原发性癌症类型的脑转移瘤中与免疫相关的基因。
一组基因在肺癌脑转移瘤的微环境中显著过表达，涵盖了检查点通路、淋巴细胞浸润和TCR共表达。特别是，免疫检查点分子PD-L1、PD-L2和IDO1在肺癌脑转移瘤中的表达水平高于其他两种癌症类型的脑转移瘤。
本研究展示了不同癌症类型脑转移瘤的免疫图谱。鉴于脑转移瘤中PD-1/PD-L1轴的高RNA表达水平和免疫浸润，探索免疫检查点阻断对颅内转移肺癌患者的疗效是值得的。
