title: An adaptive immune response driven by mature, antigen-experienced T and B cells within the microenvironment of oral squamous cell carcinoma.
abstract: Lymphocyte infiltrates have been observed in the microenvironment of oral cancer; however, little is known about whether the immune response of the lymphocyte infiltrate affects tumor biology. For a deeper understanding of the role of the infiltrating-lymphocytes in oral squamous cell carcinoma (OSCC), we characterized the lymphocyte infiltrate repertoires and defined their features. Immunohistochemistry revealed considerable T and B cell infiltrates and lymphoid follicles with germinal center-like structures within the tumor microenvironment. Flow cytometry demonstrated that populations of antigen-experienced CD4+ and CD8+ cells were present, as well as an enrichment of regulatory T cells; and T cells expressing programmed death-1 (PD-1) and T cell Ig and mucin protein-3 (Tim-3), indicative of exhaustion, within the tumor microenvironment. Characterization of tumor-infiltrating B cells revealed clear evidence of antigen exposure, in that the cardinal features of an antigen-driven B cell response were present, including somatic mutation, clonal expansion, intraclonal variation and isotype switching. Collectively, our results point to an adaptive immune response occurring within the OSCC microenvironment, which may be sustained by the expression of specific antigens in the tumor.
authors.affiliation: State Key Laboratory of Medical Genetics, School of Life Science, Central South University, Changsha, Hunan, 410013, People's Republic of China.|Research Institution of Stomatology, Xiangya Stomatological Hospital & School of Stomatology, Central South University, Changsha, Hunan, 410078, People's Republic of China.|Department of Oral Maxillofacial Surgery, Xiangya Stomatological Hospital & School of Stomatology, Central South University, Changsha, Hunan, 410078, People's Republic of China.
authors.forename: Hongzhi
authors.initials: H
authors.lastname: Quan
authors.affiliation: Department of Immunobiology, Xiangya Hospital, Central South University, Changsha, Hunan, 410078, People's Republic of China.
authors.forename: Liangjuan
authors.initials: L
authors.lastname: Fang
authors.affiliation: Research Institution of Stomatology, Xiangya Stomatological Hospital & School of Stomatology, Central South University, Changsha, Hunan, 410078, People's Republic of China.
authors.forename: Hao
authors.initials: H
authors.lastname: Pan
authors.affiliation: Research Institution of Stomatology, Xiangya Stomatological Hospital & School of Stomatology, Central South University, Changsha, Hunan, 410078, People's Republic of China.
authors.forename: Zhiyuan
authors.initials: Z
authors.lastname: Deng
authors.affiliation: Research Institution of Stomatology, Xiangya Stomatological Hospital & School of Stomatology, Central South University, Changsha, Hunan, 410078, People's Republic of China.|Department of Molecular Biology, University of Aarhus, Aarhus C, DK-8000, Denmark.
authors.forename: Shan
authors.initials: S
authors.lastname: Gao
authors.affiliation: Research Institution of Stomatology, Xiangya Stomatological Hospital & School of Stomatology, Central South University, Changsha, Hunan, 410078, People's Republic of China.
authors.forename: Ousheng
authors.initials: O
authors.lastname: Liu
authors.affiliation: Research Institution of Stomatology, Xiangya Stomatological Hospital & School of Stomatology, Central South University, Changsha, Hunan, 410078, People's Republic of China.
authors.forename: Yuehong
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Oral Maxillofacial Surgery, Xiangya Stomatological Hospital & School of Stomatology, Central South University, Changsha, Hunan, 410078, People's Republic of China.
authors.forename: Yanjia
authors.initials: Y
authors.lastname: Hu
authors.affiliation: Research Institution of Stomatology, Xiangya Stomatological Hospital & School of Stomatology, Central South University, Changsha, Hunan, 410078, People's Republic of China.|Department of Oral Maxillofacial Surgery, Xiangya Stomatological Hospital & School of Stomatology, Central South University, Changsha, Hunan, 410078, People's Republic of China.
authors.forename: Xiaodan
authors.initials: X
authors.lastname: Fang
authors.affiliation: State Key Laboratory of Medical Genetics, School of Life Science, Central South University, Changsha, Hunan, 410013, People's Republic of China.|Department of Oral Pathology, Xiangya Stomatological Hospital & School of Stomatology, Central South University, Changsha, Hunan, 410078, People's Republic of China.
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Yao
authors.affiliation: Department of Oral Maxillofacial Surgery, Xiangya Hospital, Central South University, Changsha, Hunan, 410078, People's Republic of China.
authors.forename: Feng
authors.initials: F
authors.lastname: Guo
authors.affiliation: Department of Oral Maxillofacial Surgery, Xiangya Third Hospital, Central South University, Changsha, Hunan, 410013, People's Republic of China.
authors.forename: Ruohuang
authors.initials: R
authors.lastname: Lu
authors.affiliation: State Key Laboratory of Medical Genetics, School of Life Science, Central South University, Changsha, Hunan, 410013, People's Republic of China.
authors.forename: Kun
authors.initials: K
authors.lastname: Xia
authors.affiliation: Research Institution of Stomatology, Xiangya Stomatological Hospital & School of Stomatology, Central South University, Changsha, Hunan, 410078, People's Republic of China.|Department of Oral Maxillofacial Surgery, Xiangya Stomatological Hospital & School of Stomatology, Central South University, Changsha, Hunan, 410078, People's Republic of China.
authors.forename: Zhangui
authors.initials: Z
authors.lastname: Tang
mesh_terms: D056704:Adaptive Immunity; D000595:Amino Acid Sequence; D000951:Antigens, Neoplasm / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology*; D002294:Carcinoma, Squamous Cell / Q000276:immunology*; D006801:Humans; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology; D008969:Molecular Sequence Data; D009062:Mouth Neoplasms / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D014407:Tumor Cells, Cultured; D059016:Tumor Microenvironment / Q000276:immunology*; D060152:V(D)J Recombination
chemical_list: D000951:Antigens, Neoplasm
keywords: BCR Ig repertoire; immune-microenvironment; oral squamous cell carcinoma; tumor-infiltrating lymphocytes