Development of cancer immunotherapy using tumor-associated antigen-derived long peptides and liberation from immune suppression mediated trough IL-6 signaling

2017 Fiscal Year Final Research Report

• Project/Area Number: 15H04311
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Tumor therapeutics
• Research Institution: Kumamoto University
• Principal Investigator: Nishimura Yasuharu 熊本大学, 生命資源研究・支援センター, シニア教授 (10156119)
• Co-Investigator(Kenkyū-buntansha): 入江 厚 熊本大学, 大学院生命科学研究部(医), 講師 (30250343) ; 河野 健司 大阪府立大学, 工学(系)研究科(研究院), 教授 (90215187)
• Co-Investigator(Renkei-kenkyūsha): Eto Masatoshi 九州大学, 大学院医学研究院, 教授 (90315078) ; Nakayama Hideki 熊本大学, 大学院生命科学研究部, 教授 (70381001)
• Research Collaborator: Tsukamoto Hirotake (Awai Hirotake) 熊本大学, 大学院生命科学研究部, 講師 (10433020)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: 腫瘍免疫 / 腫瘍関連抗原 / 抗原ペプチド / 細胞傷害性T細胞 / ヘルパーT細胞 / IL-6シグナル / 免疫抑制的腫瘍微小環境 / 免疫抑制解除

Outline of Final Research Achievements

We previously identified novel tumor-associated antigens (TAAs) frequently overexpressed in various cancers. In this study we identified these TAAs-derived long peptides (LPs) that can induce both Th1 cells restricted by common HLA class II molecules, and tumor-reactive CTLs specific to SPs included in LPs by cross-presentation in both human in vitro culture and HLA-transgenic mice in vivo. These LPs were naturally presented by DC and these TAA-LPs-specific Th cells were observed in cancer patients suggesting usefulness of these peptides for cancer immunotherapy. We demonstrated that tumor-specific Th1 cells was attenuated in tumor-bearing mice and cancer patients in an IL-6 and soluble IL-6 receptor (sIL-6R)-dependent manner. Abundant IL-6/sIL-6R was produced by myeloid cells in tumor-bearing mice and inhibition of IL-6-mediated signals restored the T cell-mediated tumor immunity suggesting that IL-6/sIL-6R is a rational target to augment T-cell-mediated cancer immunotherapy.

Free Research Field

免疫学