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Int J Cancer. 2016 Jun 15;138(12):2952-62. doi: 10.1002/ijc.30019. Epub 2016 Feb 23.

An adaptive immune response driven by mature, antigen-experienced T and B cells within the microenvironment of oral squamous cell carcinoma.

Quan H1,2,3, Fang L4, Pan H2, Deng Z2, Gao S2,5, Liu O2, Wang Y2, Hu Y3, Fang X2,3, Yao Z1,6, Guo F7, Lu R8, Xia K1, Tang Z2,3.

Author information

1
State Key Laboratory of Medical Genetics, School of Life Science, Central South University, Changsha, Hunan, 410013, People's Republic of China.
2
Research Institution of Stomatology, Xiangya Stomatological Hospital & School of Stomatology, Central South University, Changsha, Hunan, 410078, People's Republic of China.
3
Department of Oral Maxillofacial Surgery, Xiangya Stomatological Hospital & School of Stomatology, Central South University, Changsha, Hunan, 410078, People's Republic of China.
4
Department of Immunobiology, Xiangya Hospital, Central South University, Changsha, Hunan, 410078, People's Republic of China.
5
Department of Molecular Biology, University of Aarhus, Aarhus C, DK-8000, Denmark.
6
Department of Oral Pathology, Xiangya Stomatological Hospital & School of Stomatology, Central South University, Changsha, Hunan, 410078, People's Republic of China.
7
Department of Oral Maxillofacial Surgery, Xiangya Hospital, Central South University, Changsha, Hunan, 410078, People's Republic of China.
8
Department of Oral Maxillofacial Surgery, Xiangya Third Hospital, Central South University, Changsha, Hunan, 410013, People's Republic of China.

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.

KEYWORDS:

BCR Ig repertoire; immune-microenvironment; oral squamous cell carcinoma; tumor-infiltrating lymphocytes

PMID:
26815146
DOI:
10.1002/ijc.30019
[Indexed for MEDLINE]
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