Programmed death-ligand 1 and its soluble form are highly expressed in nasal natural killer/T-cell lymphoma: a potential rationale for immunotherapy

• DOI: 10.1007/s00262-017-1987-x
• Publication Date: 2017-03-27T16:07:38Z
• Authors: Toshihiro Nagato; Takayuki Ohkuri; Kenzo Ohara; Yui Hirata; Kan Kishibe; Yuki Komabayashi; Seigo Ueda; Miki Takahara; Takumi Kumai; Kei Ishibashi; Akemi Kosaka; Naoko Aoki; Kensuke Oikawa; Yuji Uno; Naoko Akiyama; Masatoshi Sado; Hidehiro Takei; Esteban Celis; Yasuaki Harabuchi; Hiroya Kobayashi
• Keywords: Adult; Aged, 80 and over; Male; 0301 basic medicine; Biopsy; Nose Neoplasms; Programmed Cell Death 1 Receptor; Kaplan-Meier Estimate; Middle Aged; Prognosis; B7-H1 Antigen; Disease-Free Survival; 3. Good health; Lymphoma, Extranodal NK-T-Cell; Mice; 03 medical and health sciences; Cell Line, Tumor; Animals; Heterografts; Humans; Female; Immunotherapy; Aged

Nasal natural killer/T-cell lymphoma (NNKTL) is an aggressive neoplasm with poor therapeutic responses and prognosis. The programmed death-1/programmed death-ligand 1 (PD-1/PD-L1) pathway plays an important role in immune evasion of tumor cells through T-cell exhaustion. The aim of the present study was to examine the expression of PD-L1 and PD-1 molecules in NNKTL. We detected the expression of PD-L1 in biopsy samples from all of the NNKTL patients studied. PD-L1 was found on both malignant cells and tumor-infiltrating macrophages, while PD-1-positive mononuclear cells infiltrated the tumor tissues in 36% of patients. Most significantly, soluble PD-L1 (sPD-L1) was present in sera of NNKTL patients at higher levels as compared to healthy individuals and the levels of serum sPD-L1 in patients positively correlated with the expression of PD-L1 in lymphoma cells of tumor tissues. In addition, the high-sPD-L1 group of patients showed significantly worse prognosis than the low-sPD-L1 group. Furthermore, we confirmed that membrane and soluble PD-L1 was expressed on the surface and in the culture supernatant, respectively, of NNKTL cell lines. The expression of PD-L1 was observed in tumor tissues and sera from a murine xenograft model inoculated with an NNKTL cell line. Our results suggest that sPD-L1 could be a prognostic predictor for NNKTL and open up the possibility of immunotherapy of this lymphoma using PD-1/PD-L1 axis inhibitors.