Development of novel cancer immunotherapy based on the release of immune anergic state

• Project/Area Number: 15H06878
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Single-year Grants
• Research Field: Tumor therapeutics
• Research Institution: National Cancer Center Japan
• Principal Investigator: Maeda Yuka 国立研究開発法人国立がん研究センター, 研究所, 研究員 (20757223)
• Research Collaborator: YAMAZAKI Naoya ; MORI Taisuke
• Project Period (FY): 2015-08-28 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000); Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: がん免疫療法 / 制御性T細胞 / 腫瘍免疫 / 悪性黒色腫 / 抗腫瘍免疫応答 / 不応答

Outline of Final Research Achievements

Cancer immunotherapies are now a critical category of cancer therapy. However, the clinical benefits with immune checkpoint inhibitors are observed in limited patients. Additionally, immune-related adverse effects are often experienced in the treated patients, indicating the importance to identify predictive biomarkers for both clinical responders and patients with adverse effects. As most tumor antigens are derived from self-constituents, immunological self-tolerance induced by naturally occurring Tregs may hamper the induction of effective T-cell responses. We investigated Treg-suppressed tumor (self) antigen-specific CD8+ T cells and found that Tregs rendered them anergic by inhibiting co-stimulation of antigen-presenting cells. In this study, we examined frequency, function and markers of anergic T cells in malignant melanoma patients. We then propose that the correlation of cancer immunosuppressive state (anergic state) and clinical outcome of malignant melanoma patients.

Research Products

• [Journal Article] がん免疫療法におけるT細胞応答の効果予測因子としての可能性 (2016)
  • Author(s): 前田優香
  • Journal Title: 医学の歩み がん標的分子と治療開発ー現状と将来 Volume: 258 Pages: 465-470
• [Journal Article] Two FOXP3(+)CD4(+) T cell subpopulations distinctly control the prognosis of colorectal cancers. (2016)
  • Author(s): Saito, T., Nishikawa, H., Wada, H., Nagano, Y., Sugiyama, D., Atarashi, K., Maeda, Y., Hamaguchi, M., Ohkura, N., Sato, E., Nagase, H., Nishimura, J., Yamamoto, H., Takiguchi, S., Tanoue, T., Suda, W., Morita, H., Hattori, M., Honda, K., Mori, M., Doki, Y., Sakaguchi, S.
  • Journal Title: Nat. Med Volume: 22 Issue: 6 Pages: 679-684
  • DOI: 10.1038/nm.4086
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] Predicting patient response to immune checkpoint therapies through deep immune profiling (2017)
  • Author(s): Yuka Maeda
  • Organizer: Interstellar Initiative (The New York Academy of Science)
  • Place of Presentation: The New York Academy of Science, US
  • Year and Date: 2017-03-18
  • Int'l Joint Research
• [Presentation] がん免疫療法におけるT細胞応答の効果予測因子としての可能性 (2016)
  • Author(s): 前田優香
  • Organizer: 第７５回日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜、第４会場
  • Year and Date: 2016-10-06
  • Invited
• [Presentation] Cancer antigens recognized by CD8+ T cells that induce tumor regression (2016)
  • Author(s): 前田優香
  • Organizer: 第31回名古屋国際癌治療シンポジウム
  • Place of Presentation: 愛知がんセンター、日本
  • Year and Date: 2016-02-13
  • Int'l Joint Research / Invited
• [Presentation] Regulatory T Cell-mediated Anergy Induction in Tumor-selfantigen-specific CD8+ T Cells (2015)
  • Author(s): 前田優香
  • Organizer: Society for Immunotherapy of Cancer 30th Anniversary Annual Meeting
  • Place of Presentation: National Harbor, MD, US
  • Year and Date: 2015-11-04
  • Int'l Joint Research / Invited
• [Presentation] Cancer antigens recognized by CD8+ T cells which induce tumor regression (2015)
  • Author(s): 前田優香
  • Organizer: 第74回日本癌学会学術総会
  • Place of Presentation: 名古屋国際会議場
  • Year and Date: 2015-10-08
  • Invited