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- Title
Programmed death-ligand 1 and its soluble form are highly expressed in nasal natural killer/T-cell lymphoma: a potential rationale for immunotherapy.
- Authors
Nagato, Toshihiro; Ohkuri, Takayuki; Ohara, Kenzo; Hirata, Yui; Kishibe, Kan; Komabayashi, Yuki; Ueda, Seigo; Takahara, Miki; Kumai, Takumi; Ishibashi, Kei; Kosaka, Akemi; Aoki, Naoko; Oikawa, Kensuke; Uno, Yuji; Akiyama, Naoko; Sado, Masatoshi; Takei, Hidehiro; Celis, Esteban; Harabuchi, Yasuaki; Kobayashi, Hiroya
- Abstract
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.
- Subjects
PROGRAMMED cell death 1 receptors; CANCER immunotherapy; GENE expression; T-cell lymphoma; PROGNOSIS; THERAPEUTICS
- Publication
Cancer Immunology, Immunotherapy, 2017, Vol 66, Issue 7, p877
- ISSN
0340-7004
- Publication type
Article
- DOI
10.1007/s00262-017-1987-x