Novel tumor immunotharapy for advanced lung cancer using homeostatic reconstitution of antitumor immunity

• Project/Area Number: 24591157
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Respiratory organ internal medicine
• Research Institution: Niigata University
• Principal Investigator: WATANABE Satoshi 新潟大学, 医歯学総合病院, 助教 (50529740)
• Co-Investigator(Kenkyū-buntansha): KAGAMU Hiroshi 新潟大学, 医歯学系, 准教授 (30418686) ; YOSHIZAWA Hirohisa 新潟大学, 医歯学総合病院, 特任教授 (50282984) ; NAKATA Ko 新潟大学, 医歯学総合病院, 教授 (80207802) ; MIURA Satoru 新潟大学, 医歯学総合病院, 特任助教 (70420320)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2014: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: Tumor immunotherapy / Regulatory T cells / lung cancer / 腫瘍免疫 / 肺癌 / 抑制性T細胞 / 腫瘍免疫療法 / 細胞療法 / regulatory T cell / tumor immunotherapy / lymphodepletion / regulatory T cells

Outline of Final Research Achievements

It has been well established that priming of antitumor effector T cells is augmented during recovery from lymphopenia induced by cytotoxic regimens. We found immune-suppressive cells resistant to cytotoxic therapy were increased following cytotoxic regimens. Depletion of these immune-suppressive cells using monoclonal antibodies enhanced antitumor immune responses and delayed tumor progression.
Consistant with mice model, FACS analysis of peripheral blood monocytes from advanced small cell lung cancer patients revealed increased percentage of immune-suppressive cells after chemotehrarpy. Our results show that the combination of lymphodepletion with the further inhibition of immune-suppressive cells resistant to cytotoxic therapies represent a promising approach to enhance the efficacy of tumor immunotherapies.

Research Products

• [Journal Article] Advanced thymic cancer treated with carboplatin and paclitaxel in a patient undergoing hemodialysis. (2015)
  • Author(s): Miura S, Watanabe S (他12名8番目）
  • Journal Title: Internal medicine Volume: 54 Pages: 55-58
  • NAID: 130004902998
  • Peer Reviewed
• [Journal Article] DDX3X induces primary EGFR-TKI resistance based on intratumor heterogeneity in lung cancer cells harboring EGFR-activating mutations. (2014)
  • Author(s): Nozaki K, Watanabe S (他8名8番目）
  • Journal Title: PLoS One Volume: 9
  • Peer Reviewed / Open Access
• [Journal Article] A case of thymic cancer effectively treated by weekly paclitaxel combined with carboplatin (2014)
  • Author(s): Kondo R, Watanabe S (他12名2番目）
  • Journal Title: Gan To Kagaku Ryoho Volume: 41 Pages: 2607-2609
  • Peer Reviewed
• [Journal Article] Depletion of radio-resistant regulatory T cells enhances antitumor immunity during recovery from lymphopenia. (2012)
  • Author(s): Baba J, Watanabe S, Saida Y, Tanaka T, Miyabayashi T, Koshio J, Ichikawa K, Nozaki K, Koya T, Deguchi K, Tan C, Miura S, Tanaka H, Tanaka J, Kagamu H, Yoshizawa H, Nakata K, Narita I.
  • Journal Title: Blood Volume: 120 Pages: 2417-2427
  • Peer Reviewed
• [Journal Article] Epitope diversification driven by non-tumor epitope-specific Th1 and Th17 mediates potent antitumor reactivity. (2012)
  • Author(s): Ichikawa K, Kagamu H, Koyama K, Miyabayashi T, Koshio J, Miura S, Watanabe S, Yoshizawa H, Narita I.
  • Journal Title: Vaccine Volume: 30 Pages: 6190-6197
  • Peer Reviewed
• [Presentation] Critical roles of chemo-resistant effector and regulatory T cells in antitumor immunity after cytotoxic therapy (2014)
  • Author(s): Sato K, Watanabe S(他12名中2番目）
  • Organizer: 日本癌学会
  • Place of Presentation: 横浜, パシフィコ横浜
  • Year and Date: 2014-09-25 – 2014-09-27
• [Presentation] Dendritic cell vaccination and regulatory T-cell depletion augment antitumor immunity after cytotoxic therapy (2014)
  • Author(s): Tanaka T, Watanabe S(他14名中2番目)
  • Organizer: American Association for Cancer Research
  • Place of Presentation: San Diego, USA, San Diego Convention Center
  • Year and Date: 2014-04-05 – 2014-04-09
• [Presentation] Chemo-resistant regulatory T cells suppress the development of antitumor immunity after cytotoxic regimens (2013)
  • Author(s): 才田 優
  • Organizer: Ameridan association for cancer research
  • Place of Presentation: ワシントンD.C. アメリカ
• [Presentation] Appropriate condithining of CD4 positive T cells for antitumor immunotherapy (2013)
  • Author(s): 田中 知宏
  • Organizer: Ameridan association for cancer research
  • Place of Presentation: ワシントンD.C. アメリカ
• [Presentation] 生体外で増殖・活性化したCD4+T細胞はリンパ球減少状態にある担癌宿主内の細胞障害性T細胞を介して抗腫瘍活性を示す (2013)
  • Author(s): 田中 知宏
  • Organizer: 日本癌学会
  • Place of Presentation: 横浜
• [Presentation] Successful treatment of advanced tumors with chemo-immunotherapy: a combination of cyclophosphamide and inhibition of chemo-resistant immune suppressor cells. (2012)
  • Author(s): Yu Saida, Satoshi Watanabe, Tomohiro Tanaka, Junko Baba, Koichirou Nozaki, Kosuke Ichikawa, Jun Koshio, Satoru Miura, Junta Tanaka, Hiroshi Kagamu, Hirohisa Yoshizawa, Ichiei Narita
  • Organizer: American assocation of cancer research
  • Place of Presentation: Chicago, USA
• [Presentation] Combination of cyclophosphamide and inhibition of chemo-resistant suppressor cells successfully treated advanced tumors. (2012)
  • Author(s): Yu Saida, Satoshi Watanabe, Tomohiro Tanaka, Junko Baba, Koichirou Nozaki, Kosuke Ichikawa, Jun Koshio, Satoru Miura, Junta Tanaka, Hiroshi Kagamu, Hirohisa Yoshizawa, Ichiei Narita
  • Organizer: 日本癌学会
  • Place of Presentation: 札幌