title: Expression of VISTA correlated with immunosuppression and synergized with CD8 to predict survival in human oral squamous cell carcinoma.
abstract: V-domain Ig suppressor of T cell activation (VISTA), a novel immune checkpoint regulatory molecule, suppresses T cell mediated immune responses. The aim of the present study was to profile the immunological expression, clinical significance and correlation of VISTA in human oral squamous cell carcinoma (OSCC). Human tissue microarrays, containing 165 primary OSCCs, 48 oral epithelial dysplasias and 43 normal oral mucosae, were applied to investigate the expression levels of VISTA, CD8, cytotoxic T lymphocyte-associated antigen 4 (CTLA-4), programmed death ligand 1 (PD-L1), PI3Kα p110, IL13Rα2, phospho-STAT3 at tyrosine 705 (p-STAT3) and myeloid-derived suppressor cell (MDSC) markers (CD11b and CD33) by immunohistochemistry and digital pathology analysis. The results demonstrated that the protein level of VISTA was significantly higher in human OSCC specimens, and that VISTA expression in primary OSCCs was correlated with lymph node status. VISTA expression did not serve as an independent predictor for poor prognosis, while patient subgroup with VISTA high and CD8 low expression (22/165) had significantly poorer overall survival compared with other subgroups based on the multivariate and Cox hazard analyses among the primary OSCC patients in the present cohort. Additionally, the expression of VISTA was significantly correlated with PD-L1, CTLA-4, IL13Rα2, PI3K, p-STAT3, CD11b and CD33 according to Pearson's correlation coefficient test. Taken together, the results indicated that the VISTA high and CD8 low group, as an immunosuppressive subgroup, might be associated with a poor prognosis in primary OSCC. These findings indicated that VISTA might be a potential immunotherapeutic target in OSCC treatment.
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, 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, 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, China.
authors.forename: Cong-Fa
authors.initials: CF
authors.lastname: Huang
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, 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, 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, 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, China.|Department of Oral Maxillofacial-Head Neck Oncology, School and Hospital of Stomatology, Wuhan University, Wuhan, 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, China.|Department of Oral Maxillofacial-Head Neck Oncology, School and Hospital of Stomatology, Wuhan University, Wuhan, 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, China. zhijundejia@163.com.|Department of Oral Maxillofacial-Head Neck Oncology, School and Hospital of Stomatology, Wuhan University, Wuhan, China. zhijundejia@163.com.
authors.forename: Zhi-Jun
authors.initials: ZJ
authors.lastname: Sun
mesh_terms: D060887:B7 Antigens / Q000096:biosynthesis*; D060890:B7-H1 Antigen / Q000096:biosynthesis; D016827:CD8 Antigens / Q000276:immunology*; D060908:CTLA-4 Antigen / Q000096:biosynthesis; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000276:immunology* / Q000473:pathology; D006801:Humans; D007165:Immunosuppression Therapy; D009062:Mouth Neoplasms / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D011379:Prognosis; D050796:STAT3 Transcription Factor / Q000096:biosynthesis; D016019:Survival Analysis
chemical_list: D060887:B7 Antigens; D060890:B7-H1 Antigen; C423236:CD274 protein, human; D016827:CD8 Antigens; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; C000588758:VSIR protein, human
keywords: CD8; Immune checkpoint; Oral squamous cell carcinoma; Prognosis; VISTA