Accumulation of γ/δ T Cells in Human Dysgerminoma and Seminoma: Roles in Autologous Tumor Killing and Granuloma Formation

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Abstract
The precise biological function of a subset of T cells bearing γ/δ T cell receptor (TCR) remains poorly understood. The present study demonstrated the presence of γ/δ T cells in tumor-infiltrating lymphocytes (TIL) and peripheral blood lymphocytes (PBL) of human patients with dysgerminoma and seminoma when determined by flow cytometry and in situ immunohistochemical staining. TIL contained a high percentage of γ/δ T cells, ranging from 17.3 to 35.1%. γ/δ T cells often accumulated within the granulomatous inflammation of tumor tissues. The majority of γ/δ T cells were Vγ9/Vδ2+ cells. Freshly isolated PBL, TIL and purified γ/δ T cells showed autologous tumor killing (ATK) activity, which could be inhibited by monoclonal antibodies (mAb) against Vδ2. Furthermore, two γ/δ T cell clones established from TIL showed cytotoxicity against autologous and allogeneic dysgerminoma, while they had low or no lytic effects on other cell types including carcinomas of ovary and tumor cell lines such as K562, Daudi and Molt-4. Lysis of autologous tumor cells by the clone was inhibited completely by anti-Vδ2 mAb and partially by mAb against CD3, LFA-1α and ICAM-1 molecules, while it was resistant to anti-CD8, anti-HLA-ABC and anti-HLA-DR mAb. Supernatants produced by γ/δ T cell clones induced adhesion, aggregation and increased DNA synthesis of monocytes and some characteristics of activated macrophages or epithelioid cells. Tumor necrosis factor (TNF)-α, granulocyte-macrophage colony stimulating factor (GM-CSF) and interferon (IFN)-γ were detected in the supernatants of γ/δ T cell clone. These results suggest that γ/δ T cells accumulating in dysgerminoma and seminoma exhibit ATK activity through Vγ9/δ2 TCR and these γ/δ T cells also play a role in the formation of granulomatous inflammation, which is associated with human dysgerminoma and seminoma.