Purpose: NK/T-cell neoplasms are rare, highly aggressive, and insensitive to chemotherapy. These lymphomas have a poor prognosis, with patients being vulnerable to relapse. Hence, there is a need for alternative treatments. The purpose of this study is to investigate whether anti-PD1 takes effect on NK/T cell lymphoma. Methods: The expression of PD-L1 in NK/T cell lines was investigated by flow cytometry and by Western blot. In vivo, overall survival and median survival time of mice bearing an NK/T cell line tumor was assessed. Tumor-infiltrating T cells and monocyte-derived suppressor cells were evaluated by flow cytometry. Levels of PD-L1 and components of the JAK-STAT pathway were assessed in tumor tissues by immunohistochemistry. Results: NK/T cell lines had greater expression of PD-L1 than normal peripheral blood human NK cells. In vivo, anti-PD1 treatment improved overall survival and median survival time of mice bearing an NK/T cell line. Furthermore, anti-PD1 treatment increased levels of PD-L1. Cultured tumor-infiltrating lymphocytes from mice treated with anti-PD1 had greater levels of IFN-γ than cultured lymphocytes from untreated animals. Further, levels of JAK2 and STAT1 were greater in mice treated with anti-PD1. Conclusion: In vivo, anti-PD1 inhibited the progression of an NK/T-cell lymphoma and up-regulated PD-L1 expression. This up-regulation may be through the IFN-γ-associated JAK-STAT pathway.
28 November 2018 in Journal of Cellular and Molecular Medicine
Novel nude mice model of human NK/T cell lymphoma were established by subcutaneously injecting two NK/T cell lymphoma cell lines into the right axillary region of mice and successful passages were completed by injecting cell suspension which was obtained through a 70‐μm cell strainer. These mice models and corresponding cell clones have been successfully developed for more than 8 generations. The survival rates of both resuscitation and transplantation in NKYS and YT models were 90% and 70% correspondingly. Pathologically, the tumour cells in all passages of the lymphoma‐bearing mice and cell lines obtained from tumours were parallel to initial cell lines. Immunologically, the tumour cells expressed the characteristics of the primary and essential NK/T lymphomas. The novel mice models maintained the essential features of human NK/T cell lymphoma, and they would be ideal tools in vivo for further research of human NK/T cell lymphoma.