HHLA2 Expression is Associated with Poor Survival in Patients with Hepatocellular Carcinoma

Yituo Xu,1 Zhijie Huang,1 Xingjuan Yu,1 Zhixiong Li,1 Limin Zheng,1,2 Jing Xu1 1Collaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, 510060, People’s Republic of China; 2MOE Key Laboratory of...

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Autores principales:	Xu Y, Zhijie H, Yu X, Li Z, Zheng L, Xu J
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2021
Materias:	hhla2 monocytes/macrophages hcc prognosis Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/7d6ba58db404467da628f464ba4bf014
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spelling	oai:doaj.org-article:7d6ba58db404467da628f464ba4bf0142021-12-02T15:07:50ZHHLA2 Expression is Associated with Poor Survival in Patients with Hepatocellular Carcinoma1177-5491https://doaj.org/article/7d6ba58db404467da628f464ba4bf0142021-08-01T00:00:00Zhttps://www.dovepress.com/hhla2-expression-is-associated-with-poor-survival-in-patients-with-hep-peer-reviewed-fulltext-article-BTThttps://doaj.org/toc/1177-5491Yituo Xu,1 Zhijie Huang,1 Xingjuan Yu,1 Zhixiong Li,1 Limin Zheng,1,2 Jing Xu1 1Collaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, 510060, People’s Republic of China; 2MOE Key Laboratory of Gene Function and Regulation, State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou, 510060, People’s Republic of ChinaCorrespondence: Jing Xu; Limin ZhengCollaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, 510060, People’s Republic of ChinaEmail xujing@sysucc.org.cn; zhenglm@mail.sysu.edu.cnBackground: Human endogenous retrovirus-H long terminal repeat-associating protein 2 (HHLA2) is a member of the B7 family; however, little is known regarding its expression and clinical relevance in hepatocellular carcinoma (HCC).Methods: To better characterize HHLA2 expression in HCC, we analyzed its expression by in situ staining and further investigated its correlation with immune infiltration and patient prognosis.Results: HHLA2 was primarily expressed in the peri-tumor region of HCC tissues and co-localized with CD68+ monocytes/macrophages. In vitro analysis and multi-immunofluorescence staining showed up-regulated HHLA2 expression in tumor-activated monocytes/macrophages, and HHLA2+ monocytes/macrophages expressed high levels of HLA-DR in HCC tissue. A correlation analysis showed that samples displaying high HHLA2 expression in the peri-tumor region had significant tumor infiltration of CD204+ and CD11b+ cells, and low expression of genes associated with an anti-tumor immune response. The high level of peri-tumoral HHLA2 expression was associated with a poor patient overall survival (OS; P = 0.008). A multivariate analysis revealed that HHLA2 expression in the peri-tumor region was an independent prognostic factor for OS (hazard ratio = 1.872, p = 0.003). Moreover, the expression of HHLA2 was negatively correlated with PD-L1, and patients exhibiting HHLA2 and programmed cell death-ligand 1(PD-L1) co-expression had the shortest survival time.Conclusion: HHLA2 expression represented an immunosuppressive microenvironment in HCC, and may serve as a potential target for immunotherapy.Keywords: HHLA2, monocytes/macrophages, HCC, prognosisXu YZhijie HYu XLi ZZheng LXu JDove Medical Pressarticlehhla2monocytes/macrophageshccprognosisMedicine (General)R5-920ENBiologics: Targets & Therapy, Vol Volume 15, Pp 329-341 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	hhla2 monocytes/macrophages hcc prognosis Medicine (General) R5-920
spellingShingle	hhla2 monocytes/macrophages hcc prognosis Medicine (General) R5-920 Xu Y Zhijie H Yu X Li Z Zheng L Xu J HHLA2 Expression is Associated with Poor Survival in Patients with Hepatocellular Carcinoma
description	Yituo Xu,1 Zhijie Huang,1 Xingjuan Yu,1 Zhixiong Li,1 Limin Zheng,1,2 Jing Xu1 1Collaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, 510060, People’s Republic of China; 2MOE Key Laboratory of Gene Function and Regulation, State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou, 510060, People’s Republic of ChinaCorrespondence: Jing Xu; Limin ZhengCollaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, 510060, People’s Republic of ChinaEmail xujing@sysucc.org.cn; zhenglm@mail.sysu.edu.cnBackground: Human endogenous retrovirus-H long terminal repeat-associating protein 2 (HHLA2) is a member of the B7 family; however, little is known regarding its expression and clinical relevance in hepatocellular carcinoma (HCC).Methods: To better characterize HHLA2 expression in HCC, we analyzed its expression by in situ staining and further investigated its correlation with immune infiltration and patient prognosis.Results: HHLA2 was primarily expressed in the peri-tumor region of HCC tissues and co-localized with CD68+ monocytes/macrophages. In vitro analysis and multi-immunofluorescence staining showed up-regulated HHLA2 expression in tumor-activated monocytes/macrophages, and HHLA2+ monocytes/macrophages expressed high levels of HLA-DR in HCC tissue. A correlation analysis showed that samples displaying high HHLA2 expression in the peri-tumor region had significant tumor infiltration of CD204+ and CD11b+ cells, and low expression of genes associated with an anti-tumor immune response. The high level of peri-tumoral HHLA2 expression was associated with a poor patient overall survival (OS; P = 0.008). A multivariate analysis revealed that HHLA2 expression in the peri-tumor region was an independent prognostic factor for OS (hazard ratio = 1.872, p = 0.003). Moreover, the expression of HHLA2 was negatively correlated with PD-L1, and patients exhibiting HHLA2 and programmed cell death-ligand 1(PD-L1) co-expression had the shortest survival time.Conclusion: HHLA2 expression represented an immunosuppressive microenvironment in HCC, and may serve as a potential target for immunotherapy.Keywords: HHLA2, monocytes/macrophages, HCC, prognosis
format	article
author	Xu Y Zhijie H Yu X Li Z Zheng L Xu J
author_facet	Xu Y Zhijie H Yu X Li Z Zheng L Xu J
author_sort	Xu Y
title	HHLA2 Expression is Associated with Poor Survival in Patients with Hepatocellular Carcinoma
title_short	HHLA2 Expression is Associated with Poor Survival in Patients with Hepatocellular Carcinoma
title_full	HHLA2 Expression is Associated with Poor Survival in Patients with Hepatocellular Carcinoma
title_fullStr	HHLA2 Expression is Associated with Poor Survival in Patients with Hepatocellular Carcinoma
title_full_unstemmed	HHLA2 Expression is Associated with Poor Survival in Patients with Hepatocellular Carcinoma
title_sort	hhla2 expression is associated with poor survival in patients with hepatocellular carcinoma
publisher	Dove Medical Press
publishDate	2021
url	https://doaj.org/article/7d6ba58db404467da628f464ba4bf014
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HHLA2 Expression is Associated with Poor Survival in Patients with Hepatocellular Carcinoma

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