title: B7-H4 expression indicates poor prognosis of oral squamous cell carcinoma.
abstract: Checkpoint blockade therapy utilizing monoclonal antibodies to reactivate T cells and recover their antitumor activity makes an epoch in cancer immunotherapy. The role of B7-H4, a novel negative immune checkpoint, in oral squamous cell carcinoma (OSCC) has still not been elucidated. In this study, tissue samples from human OSCC, which contains 165 primary OSCC, 48 oral epithelial dysplasia and 43 normal oral mucosa specimens, and Tgfbr1/Pten 2cKO mice OSCC model were stained with B7-H4 antibody to analyze the correlations between B7-H4 expression and clinicopathological characteristics. Kaplan-Meier analysis was used to compare the survival of patients with high B7-H4 expression and patients with low B7-H4 expression. We found B7-H4 is highly expressed in human OSCC tissue, and the B7-H4 expression level was associated with the clinicopathological parameters containing pathological grade and lymph node status. Moreover, we confirmed that B7-H4 was overexpressed in Tgfbr1/Pten 2cKO mice OSCC model. Our data also indicated that patients with high B7-H4 expression had poor overall survival compared with those with low B7-H4 expression. Furthermore, this study demonstrated that B7-H4 was positively associated with PD-L1, CD11b, CD33, PI3Kα p110, and p-S6 (S235/236). Taken together, these findings suggest B7-H4 is a potential target in the treatment of OSCC.
authors.affiliation: The State Key Laboratory Breeding Base of Basic Science of Stomatology and Key Laboratory of Oral Biomedicine, Ministry of Education, Wuhan University, Wuhan, People's Republic of China.
authors.forename: Lei
authors.initials: L
authors.lastname: Wu
authors.affiliation: The State Key Laboratory Breeding Base of Basic Science of Stomatology and Key Laboratory of Oral Biomedicine, Ministry of Education, Wuhan University, Wuhan, People's Republic of China.
authors.forename: Wei-Wei
authors.initials: WW
authors.lastname: Deng
authors.affiliation: The State Key Laboratory Breeding Base of Basic Science of Stomatology and Key Laboratory of Oral Biomedicine, Ministry of Education, Wuhan University, Wuhan, People's Republic of China.
authors.forename: Guang-Tao
authors.initials: GT
authors.lastname: Yu
authors.affiliation: The State Key Laboratory Breeding Base of Basic Science of Stomatology and Key Laboratory of Oral Biomedicine, Ministry of Education, Wuhan University, Wuhan, People's Republic of China.
authors.forename: Liang
authors.initials: L
authors.lastname: Mao
authors.affiliation: The State Key Laboratory Breeding Base of Basic Science of Stomatology and Key Laboratory of Oral Biomedicine, Ministry of Education, Wuhan University, Wuhan, People's Republic of China.
authors.forename: Lin-Lin
authors.initials: LL
authors.lastname: Bu
authors.affiliation: The State Key Laboratory Breeding Base of Basic Science of Stomatology and Key Laboratory of Oral Biomedicine, Ministry of Education, Wuhan University, Wuhan, People's Republic of China.
authors.forename: Si-Rui
authors.initials: SR
authors.lastname: Ma
authors.affiliation: The State Key Laboratory Breeding Base of Basic Science of Stomatology and Key Laboratory of Oral Biomedicine, Ministry of Education, Wuhan University, Wuhan, People's Republic of China.|Department of Oral Maxillofacial-Head Neck Oncology, School and Hospital of Stomatology, Wuhan University, 237 Luoyu Road, Wuhan, 430079, Hubei Province, People's Republic of China.
authors.forename: Bing
authors.initials: B
authors.lastname: Liu
authors.affiliation: The State Key Laboratory Breeding Base of Basic Science of Stomatology and Key Laboratory of Oral Biomedicine, Ministry of Education, Wuhan University, Wuhan, People's Republic of China.|Department of Oral Maxillofacial-Head Neck Oncology, School and Hospital of Stomatology, Wuhan University, 237 Luoyu Road, Wuhan, 430079, Hubei Province, People's Republic of China.
authors.forename: Wen-Feng
authors.initials: WF
authors.lastname: Zhang
authors.affiliation: The State Key Laboratory Breeding Base of Basic Science of Stomatology and Key Laboratory of Oral Biomedicine, Ministry of Education, Wuhan University, Wuhan, People's Republic of China. sunzj@whu.edu.cn.|Department of Oral Maxillofacial-Head Neck Oncology, School and Hospital of Stomatology, Wuhan University, 237 Luoyu Road, Wuhan, 430079, Hubei Province, People's Republic of China. sunzj@whu.edu.cn.
authors.forename: Zhi-Jun
authors.initials: ZJ
authors.lastname: Sun
mesh_terms: D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D005260:Female; D006258:Head and Neck Neoplasms / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008198:Lymph Nodes / Q000473:pathology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009062:Mouth Neoplasms / Q000378:metabolism* / Q000473:pathology; D060787:Neoplasm Grading; D000077195:Squamous Cell Carcinoma of Head and Neck; D016019:Survival Analysis; D046888:Tissue Array Analysis; D060907:V-Set Domain-Containing T-Cell Activation Inhibitor 1 / Q000096:biosynthesis*
chemical_list: D060907:V-Set Domain-Containing T-Cell Activation Inhibitor 1; C475826:VTCN1 protein, human; C475824:Vtcn1 protein, mouse
keywords: B7-H4; Immune checkpoint; Immunotherapy; Oral squamous cell carcinoma; Tissue microarray; Transgenic mice