Anti-PD1 up-regulates PD-L1 expression and inhibits T-cell lymphoma progression: possible involvement of an IFN-γ-associated JAK-STAT pathway

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-gamma 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-gamma-associated JAK-STAT pathway.