干旱区生态环境知识资源中心(Arid): Immunogenomic characterization in gastric cancer identifies microenvironmental and immunotherapeutically relevant gene signatures

Arid

DOI	10.1002/iid3.539
	Immunogenomic characterization in gastric cancer identifies microenvironmental and immunotherapeutically relevant gene signatures
	Han, Xiao; Lu, Heyue; Tang, Xiaojun; Zhao, Yao; Liu, Hongxue
通讯作者	Liu, HX (corresponding author), Nanjing Med Univ, Affiliated Huaian 1 Peoples Hosp, Dept Obstet, Huaian, Jiangsu, Peoples R China.
来源期刊	IMMUNITY INFLAMMATION AND DISEASE
EISSN	2050-4527
出版年	2022
英文摘要	Background: Multiple molecular subtypes with distinct clinical outcomes in gastric cancer have been identified. Nonetheless, the immunogenomic subtypes of gastric cancer and its mediated tumor microenvironment (TME) characterizations have not been fully understood. Methods: Six gastric cancer cohorts with 1506 samples were obtained. Unsupervised methods were used to perform immunogenomic phenotype clustering. The least absolute shrinkage and selection operator regression method was used to construct immunogenomic characterization score (IGCS). Results: Three distinct immunogenomic phenotypes were determined. We observed a prominent survival difference between three phenotypes. The TME cell-infiltrating characteristics under these three phenotypes were highly consistent with three immune subtypes of tumors. Cluster 1, was characterized by the immune-desert phenotype, with relatively lower cell infiltration level (type 1 cold tumor); Cluster 2, characterized by immune-inflamed phenotype, with abundant innate and adaptive immune cell infiltration (hot tumor); Cluster 3, characterized by immune-excluded phenotype, with significant stromal activation and inactivated immune cell infiltration (type 2 cold tumor). We demonstrated IGCS signature was significantly correlated with TME inflammation and stroma activity, molecular subtypes, genetic variation, microsatellite instability, immune checkpoint molecules, and patient prognosis. High IGCS subtype, with poorer survival and enhanced stromal activity, presented an immune-exclusion and non-inflamed TME characterization. Low IGCS, related to increased mutation/neoantigen load and microsatellite instability, showed enhanced responses to anti-checkpoint immunotherapy. Four immunotherapy cohorts confirmed patients with low IGCS exhibited prominently enhanced clinical responses and treatment advantages. Conclusions: This study demonstrated the immunogenomic characterizations could play a crucial role in shaping the complexity and diversity of tumor microenvironment. Targeting tumor immunogenomic characteristic in order for changing adverse phenotypes may contribute to exploiting the novel immunotherapy combination strategies or novel immunotherapeutic drugs, and promoting the advance of tumor personalized immunotherapy.
英文关键词	immune checkpoint immunogenomic phenotype immunotherapy prognosis tumor microenvironment
类型	Article
语种	英语
开放获取类型	gold
收录类别	SCI-E
WOS记录号	WOS:000700824200001
WOS关键词	TUMOR PROGRESSION ; CELLS ; EXCLUSION ; BLOCKADE ; IMMUNITY ; SUBTYPES ; THERAPY ; REVEAL
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/2XILL650/363574
作者单位	[Han, Xiao; Tang, Xiaojun; Zhao, Yao] Nanjing Med Univ, Dept Gastrointestinal Surg, Affiliated Huaian 1 Peoples Hosp, Huaian, Jiangsu, Peoples R China; [Lu, Heyue] Nanjing Med Univ, Clin Med, Affiliated Huaian 1 Peoples Hosp, Huaian, Jiangsu, Peoples R China; [Liu, Hongxue] Nanjing Med Univ, Affiliated Huaian 1 Peoples Hosp, Dept Obstet, Huaian, Jiangsu, Peoples R China
推荐引用方式 GB/T 7714	Han, Xiao,Lu, Heyue,Tang, Xiaojun,et al. Immunogenomic characterization in gastric cancer identifies microenvironmental and immunotherapeutically relevant gene signatures[J],2022.
APA	Han, Xiao,Lu, Heyue,Tang, Xiaojun,Zhao, Yao,&Liu, Hongxue.(2022).Immunogenomic characterization in gastric cancer identifies microenvironmental and immunotherapeutically relevant gene signatures.IMMUNITY INFLAMMATION AND DISEASE.
MLA	Han, Xiao,et al."Immunogenomic characterization in gastric cancer identifies microenvironmental and immunotherapeutically relevant gene signatures".IMMUNITY INFLAMMATION AND DISEASE (2022).