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

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

Research output: Contribution to journalArticle

49 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)877-890
Number of pages14
JournalCancer Immunology, Immunotherapy
Volume66
Issue number7
DOIs
StatePublished - Jul 1 2017

Keywords

  • Immunotherapy
  • Nasal NK/T-cell lymphoma
  • PD-1
  • PD-L1
  • Soluble form

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Oncology
  • Cancer Research

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    Nagato, T., Ohkuri, T., Ohara, K., Hirata, Y., Kishibe, K., Komabayashi, Y., Ueda, S., Takahara, M., Kumai, T., Ishibashi, K., Kosaka, A., Aoki, N., Oikawa, K., Uno, Y., Akiyama, N., Sado, M., Takei, H., Celis, E., Harabuchi, Y., & Kobayashi, H. (2017). Programmed death-ligand 1 and its soluble form are highly expressed in nasal natural killer/T-cell lymphoma: a potential rationale for immunotherapy. Cancer Immunology, Immunotherapy, 66(7), 877-890. https://doi.org/10.1007/s00262-017-1987-x