Genomic profiles and tumor immune microenvironment of primary lung carcinoma and brain oligo-metastasis

doi:10.1038/s41419-021-03410-7

	Genomic profiles and tumor immune microenvironment of primary lung carcinoma and brain oligo-metastasis
	Song, Zhengbo 1,2; Yang, Ling 3; Zhou, Zhipeng 3; Li, Pansong 3; Wang, Wenxian 1; Cheng, Guoping 2,4; Chen, Rongrong 3; Chang, Lianpeng 3; Zhang, Yiping 1; Guan, Yanfang 3
刊名	CELL DEATH & DISEASE
	2021-01-21
卷号	12
ISSN号	2041-4889
DOI	10.1038/s41419-021-03410-7
通讯作者	Song, Zhengbo(songzb@zjcc.org.cn) ; Zhou, Rongrong(zhourr@zjcc.org.cn) ; Chen, Ming(chenming@zjcc.org.cn)
英文摘要	Brain metastasis (BM) is a common malignant event in lung cancer. Here, we recruited 33 lung cancer patients with brain oligo-metastasis to explore the genomic features and tumor immune microenvironment (TIME) of the lung and BM independently. For genomic profiling, targeted sequencing was performed. We found that high-frequent ZFHX3 occurred in the lung (40%) and brain tumor (28%), which might relate to brain metastasis event; the vast majority of patients had lesions-shared mutations in primary tumor and BM, confirming the common clonal events; and EGFR was the most frequently clonal gene in both lung and BM, indicating its driver capability. To characterize TIME status, we also sequenced the T cell receptor (TCR) repertoires and performed immunohistochemistry (IHC) on CD8+ tumor-infiltrating lymphocytes (TILs) and PD-L1 expression in 28 patients who had paired samples. Through the comparison, the TCR clonality of BM was higher than lung tumor, indicating the distinct pattern of the stronger oligoclonal T cell expansion in BM; the primary tumor had a higher TMB than oligo-BM (13.9 vs 8.7 mutations, p=0.019); CD8+TILs of BM were significantly lower than lung tumor (10% vs 30%, p=0.015), revealing the lower level of cytotoxic T cell infiltration; BM showed statistically equivalent level of PD-L1 compared with lung tumor (p=0.722). We further investigated the potential biomarkers associated with overall survival (OS) after brain surgery. We found that higher TCR clonality was related to prolonged OS in EGFR-treated patients (HR 0.175, p<0.001) but the worse outcomes in non-EGFR-treated (HR 2.623, p=0.034). More CD8+ TILs were an independently positive indicator for OS, in EGFR-treated (HR 0.160, p=0.001) and non-EGFR-treated patients (HR 0.308, p=0.009). These findings provide a meaningful molecular and clinical understanding of lung carcinoma and brain oligo-metastasis.
资助项目	National Natural Science Foundation of China[81802276] ; National Natural Science Foundation of China[81770928] ; Natural Science Foundation of Hunan[2018JJ2626]
WOS关键词	CANCER ; MANAGEMENT ; SURGERY
WOS研究方向	Cell Biology
语种	英语
出版者	SPRINGERNATURE
WOS记录号	WOS:000681135900002
资助机构	National Natural Science Foundation of China ; Natural Science Foundation of Hunan
内容类型	期刊论文
源URL	[http://ir.hfcas.ac.cn:8080/handle/334002/123072]
专题	中国科学院合肥物质科学研究院
通讯作者	Song, Zhengbo; Zhou, Rongrong; Chen, Ming
作者单位	1.Univ Chinese Acad Sci, Zhejiang Canc Hosp, Canc Hosp, Dept Clin Trial, Hangzhou 310022, Zhejiang, Peoples R China 2.Chinese Acad Sci, Inst Basic Med & Canc, Hangzhou 310022, Zhejiang, Peoples R China 3.Geneplus Beijing Inst, Beijing 102206, Peoples R China 4.Univ Chinese Acad Sci, Zhejiang Canc Hosp, Canc Hosp, Dept Pathol, Hangzhou 310022, Zhejiang, Peoples R China 5.Cent South Univ, Xiangya Hosp, Dept Oncol, Changsha 410008, Hunan, Peoples R China 6.Univ Chinese Acad Sci, Zhejiang Canc Hosp, Canc Hosp, Dept Radiotherapy, Hangzhou 310022, Zhejiang, Peoples R China
推荐引用方式 GB/T 7714	Song, Zhengbo,Yang, Ling,Zhou, Zhipeng,et al. Genomic profiles and tumor immune microenvironment of primary lung carcinoma and brain oligo-metastasis[J]. CELL DEATH & DISEASE,2021,12.
APA	Song, Zhengbo.,Yang, Ling.,Zhou, Zhipeng.,Li, Pansong.,Wang, Wenxian.,...&Chen, Ming.(2021).Genomic profiles and tumor immune microenvironment of primary lung carcinoma and brain oligo-metastasis.CELL DEATH & DISEASE,12.
MLA	Song, Zhengbo,et al."Genomic profiles and tumor immune microenvironment of primary lung carcinoma and brain oligo-metastasis".CELL DEATH & DISEASE 12(2021).