Immunomonitoring in gastrointesrinal cancer patients for development of chemoimmunotherapy

2016 Fiscal Year Annual Research Report

• Project/Area Number: 26460981
• Research Institution: National Cancer Center Japan
• Principal Investigator: 北野 滋久 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
• Keywords: 腫瘍免疫学 / がん免疫療法 / バイオマーカー

Outline of Annual Research Achievements

本研究において、標準化学療法を実施された進行消化器がん患者について免疫応答解析を実施した。初回標準化学療法を実施された大腸癌患者において治療前のmonocytic MDSC(myeloid-derived suppressor cell)、およびエフェクターメモリーT細胞の数量と PFSとの関連を認めた。（Tada, K, Kitano S, et al, Cancer Immunology Research, 2016.）さらに、化学療法を施行された進行胃癌患者においてはgranulocytic MDSCの数量とPFSの相関を見出し報告した。(Shoji H, Kitano S, et al. Oncotarget. In press.)さらに、他の癌腫（悪性黒色腫、食道がん、子宮頸癌、前立腺癌などにおいても、末梢血、腫瘍局所レベルで免疫抑制細胞(MDSC, TAM(tumor associated macrophage)やエフェクター細胞の数量、および、それらの比によって治療効果（OS, PFS）との相関を見いだすことができた。また、がん患者由来のMDSCに強発現している分子の同定も行うことができた。本研究の成果をもとに、今後の併用療法の戦略として免疫抑制細胞とそれに関わる液性因子を解除する効果を持つ薬剤を含む併用療法がが抗腫瘍効果を増強し、治療成績の向上に寄与するか否か各種がんで前向き試験で検証を進めていきたいと考えている。

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) 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 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 Pages: 47252-47264
  • DOI: https://doi.org/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) 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) Pages: 4115-4122
  • DOI: https://doi.org/10.1245/s10434-016-5354-5
  • Peer Reviewed / Acknowledgement Compliant
• [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
  • Year and Date: 2016-10-22 – 2016-10-22
  • 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
  • Year and Date: 2016-10-20 – 2016-10-20
  • 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
  • Year and Date: 2016-10-13 – 2016-10-13
  • Invited
• [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 – 2016-10-11
  • Int'l Joint Research
• [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
  • Year and Date: 2016-07-29 – 2016-07-29
  • Invited
• [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 – 2016-06-07
  • Int'l Joint Research