Immunomonitoring in gastrointesrinal cancer patients for development of chemoimmunotherapy

• Project/Area Number: 26460981
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: National Cancer Center Japan
• Principal Investigator: Kitano Shigehisa 国立研究開発法人国立がん研究センター, 早期・探索臨床研究センター, 医員 (60402682)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); 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); Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 腫瘍免疫学 / がん免疫療法 / バイオマーカー / 免疫応答解析 / 骨髄由来抑制細胞 / 大腸がん / 化学療法 / 腫瘍免疫 / 免疫療法

Outline of Final Research Achievements

Immune monitoring revealed that the number of monocytic MDSC (myeloid - derived suppressor cell) and effector memory T cells before treatment was associated with PFS. In advanced gastric cancer patients who underwent standard chemotherapy the number of granulocytic MDSC was associated with PFS. In addition, by immune analysis of peripheral blood and tumor local site in the other cancer patients (malignant melanoma, esophageal cancer, cervical cancer, prostate cancer etc.), the number of MDSC, tumor associated macrophage (TAM;M2 type) and effector cells, and their ratio was associated with clinical benefit (OS, PFS). In this study, we also have detected candidate of the molecular target on MDSC. As the next treatment strategy, it is worth trying evaluation of combination immunotherapy including reagents to suppress immunosuppressive cells and/or its related factors will contribute to enhance antitumor effect and to improve OS or not.

Research Products

• [Journal Article] Pretreatment Immune Status Correlates with Progression-Free Survival in Chemotherapy-Treated Metastatic Colorectal Cancer Patients. (2016)
  • Author(s): Tada K, Kitano S, Shoji H, Nishimura T, Shimada Y, Nagashima K, Aoki K, Hiraoka N, Honma Y, Iwasa S, Okita N, Takashima A, Kato K, Yamada Y, Katayama N, Boku N, Heike Y, Hamaguchi T.
  • Journal Title: Cancer immunology research Volume: 4(7) Issue: 7 Pages: 592-599
  • DOI: 10.1158/2326-6066.cir-15-0298
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Nivolumab for advanced melanoma: pretreatment prognostic factors and early outcome markers during therapy. (2016)
  • Author(s): Nakamura Y, Kitano S, Takahashi A, Tsutsumida A, Namikawa K, Tanese K, Abe T, Funakoshi T, Yamamoto N, Amagai M, Yamazaki N.
  • Journal Title: Oncotarget Volume: 7 Issue: 47 Pages: 77404-77415
  • DOI: 10.18632/oncotarget.12677
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Comprehensive immunohistochemical analysis of tumor microenvironment immune status in esophageal squamous cell carcinoma. (2016)
  • Author(s): Hatogai K, Kitano S, Fujii S, Kojima T, Daiko H, Nomura S, Yoshino T, Ohtsu A, Takiguchi Y, Doi T, Ochiai A.
  • Journal Title: Oncotarget Volume: 7 Issue: 30 Pages: 47252-47264
  • DOI: 10.18632/oncotarget.10055
  • Peer Reviewed / Open Access
• [Journal Article] Comparison of tumor-infiltrating lymphocytes between primary and metastatic tumors in breast cancer patients. (2016)
  • Author(s): Ogiya R, Niikura N, Kumaki N, Bianchini G, Kitano S, Iwamoto T, Hayashi N, Yokoyama K, Oshitanai R, Terao M, Morioka T, Tsuda B, Okamura T, Saito Y, Suzuki Y, Tokuda Y.
  • Journal Title: Cancer Science Volume: 107(12) Issue: 12 Pages: 1730-1735
  • DOI: 10.1111/cas.13101
  • Peer Reviewed / Open Access
• [Journal Article] High Absolute Monocyte Count Predicts Poor Clinical Outcome in Patients with Castration-Resistant Prostate Cancer Treated with Docetaxel Chemotherapy. (2016)
  • Author(s): Shigeta K, Kosaka T, Kitano S, Yasumizu Y, Miyazaki Y, Mizuno R, Shinojima T, Kikuchi E, Miyajima A, Tanoguchi H, Hasegawa S, Oya M.
  • Journal Title: Annals of Surgical Oncology Volume: 23(12) Issue: 12 Pages: 4115-4122
  • DOI: 10.1245/s10434-016-5354-5
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Pretreatment immune status correlates with progression-free survival in chemotherapy-treated metastatic colorectal cancer patients (2016)
  • Author(s): Tada K, Kitano S, Shoji H, Nishimura T, Shimada Y, Nagashima K, Aoki K, Hiraoka N, Honma Y, Iwasa S, Okita N, Takashima A, Kato K, Yamada Y, Katayama N, Boku N, Heike Y, Hamaguchi T.
  • Journal Title: Cancer Immunology Research Volume: In Press
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Presentation] Pretreatment prognostic factors and early markers for outcome in advanced melanoma treated with nivolumab (2016)
  • Author(s): Nakamura Y, Kitano S, Takahashi A, Tsutsumida A, Namikawa K, Muto M, Ueno Y, Muto N, Yamazaki N.
  • Organizer: 2016 ESCO annual meeting
  • Place of Presentation: コペンハーゲン、デンマーク
  • Year and Date: 2016-10-07
  • Int'l Joint Research
• [Presentation] Tumor-infiltrating CD204+ M2 macrophages compared to T cells as a prognosticator for patients with uterine cervical adenocarcinoma. (2016)
  • Author(s): Kawachi A, Yoshida H, Kitano S, Hiraoka S.
  • Organizer: 2017 ASCO annual meeting
  • Place of Presentation: シカゴ、米国
  • Year and Date: 2016-06-03
  • Int'l Joint Research
• [Presentation] バイオマーカーによる最適化免疫療法 (2016)
  • Author(s): 北野滋久
  • Organizer: 第54回日本癌治療学会学術集会
  • Place of Presentation: 横浜
  • Invited
• [Presentation] Immunomonitoring in Cancer Immunotheraphy (2016)
  • Author(s): Shigehisa Kitano
  • Organizer: 第54回日本癌治療学会学術集会
  • Place of Presentation: 横浜
  • Invited
• [Presentation] Clinical Development of Immune Checkpoint Inhibitors and Translational Research. (2016)
  • Author(s): Shigehisa Kitano
  • Organizer: 第78回日本血液学会総会
  • Place of Presentation: 横浜
  • Invited
• [Presentation] 免疫抑制因子の解除と複合免疫療法 (2016)
  • Author(s): 北野滋久
  • Organizer: 第20回日本がん免疫学会総会
  • Place of Presentation: 大阪
  • Invited
• [Presentation] Identification of an immunological prognostic factor for metastatic colorectal cancer patients treated with first-line oxaliplatin-based chemotherapy (2015)
  • Author(s): Tada K, Shoji H, Kitano S, T, Shimada Y, Nagashima K, Aoki K, Hiraoka N, Honma Y, Iwasa S, Okita N, Takashima A, Kato K, Yamada Y, Katayama N, Boku N, Heike Y, Hamaguchi T.
  • Organizer: European Cancer Congress 2015
  • Place of Presentation: Vienna, Austria
  • Year and Date: 2015-09-25
  • Int'l Joint Research
• [Presentation] Association between the peripheral immune status of granulocytic myeloid-derived suppressor cells and progression-free survival chemotherapy (2015)
  • Author(s): Shoji H, Heike Y, Tada K, Kitano S, Nishimura T, Shimada Y, Nagashima K, Aoki K, Hiraoka N, Honma Y, Iwasa S, Okita N, Takashima A, Kato K, Yamada Y, Katayama N, Boku N, Hamaguchi T.
  • Organizer: European Cancer Congress 2015
  • Place of Presentation: Vienna, Austria
  • Year and Date: 2015-09-25
  • Int'l Joint Research
• [Book] Tregによる免疫反応の制御とimmune checkpointによる免疫修飾の違い (2014)
  • Author(s): 北野滋久、塚崎邦弘
  • Total Pages: 6
  • Publisher: 科学療法社