干旱区生态环境知识资源中心(Arid): Landscape of Immune Microenvironment Under Immune Cell Infiltration Pattern in Breast Cancer

Arid

DOI	10.3389/fimmu.2021.711433
	Landscape of Immune Microenvironment Under Immune Cell Infiltration Pattern in Breast Cancer
	Xu, Qianhui; Chen, Shaohuai; Hu, Yuanbo; Huang, Wen
通讯作者	Huang, W (corresponding author), Wenzhou Med Univ, Affiliated Hosp 2, Dept Nephrol, Wenzhou, Peoples R China. ; Huang, W (corresponding author), Wenzhou Med Univ, Yuying Childrens Hosp, Wenzhou, Peoples R China.
来源期刊	FRONTIERS IN IMMUNOLOGY
ISSN	1664-3224
出版年	2021
卷号	12
英文摘要	Background Increasing evdence supports the suggestion that the immune cell infiltration (ICI) patterns play a pivotal role in tumor progression in breast cancer (BRCA). Nonetheless, there has been no comprehensive analysis of the ICI patterns effects on the clinical outcomes and immunotherapy. Methods Multiomic data for BRCA samples were downloaded from TCGA. ESTIMATE algorithm, ssGSEA method, and CIBERSORT analysis were used to uncover the landscape of the tumor immune microenvironment (TIME). BRCA subtypes based on the ICI pattern were identified by consensus clustering and principal-component analysis was performed to obtain the ICI scores to quantify the ICI patterns in individual tumors. Their prognostic value was validated by the Kaplan-Meier survival curves. Gene set enrichment analysis (GSEA) was applied for functional annotation. Immunophenoscore (IPS) was employed to explore the immunotherapeutic role of the ICI scores. Finally, the mutation data was analyzed by using the maftools R package. Results Three different immune infiltration patterns with a distinct prognosis and biological signature were recognized among 1,198 BRCA samples. The characteristics of TIME under these three patterns were highly consistent with three known immune profiles: immune- excluded, immune-desert, and immune-inflamed phenotypes, respectively. The identification of the ICI patterns within individual tumors based on the ICI score, developed under the ICI-related signature genes, contributed into dissecting biological processes, clinical outcome, immune cells infiltration, immunotherapeutic effect, and genetic variation. High ICI score subtype, characterized with a suppression of immunity, suggested an immune-exhausted phenotype. Abundant effective immune cells were discovered in the low ICI score patients, which corresponded to an immune-activated phenotype and might present an immunotherapeutic advantage. Immunophenoscore was implemented as a surrogate of immunotherapeutic outcome, low-ICI scores samples obtained a significantly higher immunophenoscore. Enrichment of the JAK/STAT and VEGF signal pathways were activated in the ICI low-score subgroup. Finally, the synergistic effect between the ICI score and the tumor mutation burden (TMB) was confirmed. Conclusion This work comprehensively elucidated that the ICI patterns served as an indispensable player in complexity and diversity of TIME. Quantitative identification of the ICI patterns in individual tumor will contribute into mapping the landscape of TIME further optimizing precision immunotherapy.
英文关键词	breast cancer tumor immune microenvironment immune cell infiltration immunotherapy prognosis
类型	Article
语种	英语
开放获取类型	Green Published, gold
收录类别	SCI-E
WOS记录号	WOS:000717430700001
WOS关键词	CD4(+) T-CELLS ; IFN-GAMMA ; LYMPHOCYTES ; EXPRESSION ; BLOCKADE ; ANTI-PD-1 ; THERAPY ; PD-L1 ; SENSITIVITY ; EXPANSION
WOS类目	Immunology
WOS研究方向	Immunology
资源类型	期刊论文
条目标识符	http://119.78.100.177/qdio/handle/2XILL650/368513
作者单位	[Xu, Qianhui; Chen, Shaohuai; Hu, Yuanbo; Huang, Wen] Wenzhou Med Univ, Affiliated Hosp 2, Dept Nephrol, Wenzhou, Peoples R China; [Xu, Qianhui; Chen, Shaohuai; Hu, Yuanbo; Huang, Wen] Wenzhou Med Univ, Yuying Childrens Hosp, Wenzhou, Peoples R China; [Xu, Qianhui] Zhejiang Univ, Affiliated Hosp 2, Sch Med, Dept Surg, Hangzhou, Peoples R China
推荐引用方式 GB/T 7714	Xu, Qianhui,Chen, Shaohuai,Hu, Yuanbo,et al. Landscape of Immune Microenvironment Under Immune Cell Infiltration Pattern in Breast Cancer[J],2021,12.
APA	Xu, Qianhui,Chen, Shaohuai,Hu, Yuanbo,&Huang, Wen.(2021).Landscape of Immune Microenvironment Under Immune Cell Infiltration Pattern in Breast Cancer.FRONTIERS IN IMMUNOLOGY,12.
MLA	Xu, Qianhui,et al."Landscape of Immune Microenvironment Under Immune Cell Infiltration Pattern in Breast Cancer".FRONTIERS IN IMMUNOLOGY 12(2021).