Combinatorial Immunotherapy of poly-IC and anti-PD-L1 antibody for head and neck malignancies

• Project/Area Number: 15K20172
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Otorhinolaryngology
• Research Institution: Asahikawa Medical College
• Principal Investigator: NAGATO Toshihiro 旭川医科大学, 医学部, 助教 (80431419)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2015: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: poly-IC / PD-L1 / PD-1 / 頭頸部悪性腫瘍 / 扁平上皮癌 / 鼻性NK/T細胞リンパ腫 / NK/T細胞リンパ腫 / 癌免疫療法 / 免疫アジュバント / 免疫チェックポイント

Outline of Final Research Achievements

We detected the expression of PD-L1 in biopsy samples from nasal NK/T-cell lymphoma (NNKTL) patients. PD-L1 was found on both malignant cells and tumor-infiltrating macrophages, while PD-1-positive mononuclear cells also infiltrated the tumor tissues. Most significantly, soluble PD-L1 (sPD-L1) was present in sera of NNKTL patients at higher levels as compared to healthy individuals. 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.

Research Products

• [Journal Article] Programmed death-ligand 1 and its soluble form are highly expressed in nasal natural killer/T-cell lymphoma: a potential rationale for immunotherapy (2017)
  • Author(s): 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
  • Journal Title: Cancer Immunol Immunother Volume: 印刷中 Issue: 7 Pages: 877-890
  • DOI: 10.1007/s00262-017-1987-x
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Presentation] 鼻性NK/T細胞リンパ腫に対する革新的免疫療法の開発 (2017)
  • Author(s): 長門利純
  • Organizer: 第35回日本耳鼻咽喉科免疫アレルギー学会
  • Place of Presentation: 北海道旭川市
  • Year and Date: 2017-04-13
• [Presentation] 鼻性NK/T細胞リンパ腫におけるPD-L1の発現 (2016)
  • Author(s): 長門利純、大栗敬幸、大原賢三、平田 結、岸部 幹、石橋 佳、小坂 朱、及川賢輔、熊井琢美、高原 幹、原渕保明、小林博也
  • Organizer: 第75回日本癌学会学術総会
  • Place of Presentation: 神奈川県横浜市
  • Year and Date: 2016-10-06
• [Presentation] 鼻性NK/T細胞リンパ腫におけるPD-L1の発現 (2016)
  • Author(s): 長門利純、大原賢三、平田 結、岸部 幹、駒林優樹、熊井琢美、上田征吾、高原 幹、小林博也、原渕保明
  • Organizer: 第117回日本耳鼻咽喉科学会通常総会・学術講演会
  • Place of Presentation: 愛知県名古屋市
  • Year and Date: 2016-05-18