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Development of combined immunotherapy targeting tumor-infiltrating myeloid cells for oral cancer

Research Project

Project/Area Number 19K24088
Research Category

Grant-in-Aid for Research Activity Start-up

Allocation TypeMulti-year Fund
Review Section 0907:Oral science and related fields
Research InstitutionUniversity of Toyama

Principal Investigator

Tachinami Hidetake  富山大学, 附属病院, 医員 (30850268)

Project Period (FY) 2019-08-30 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords口腔癌 / 腫瘍免疫 / 免疫チェックポイント阻害剤 / 骨髄抑制性細胞 / 口腔扁平上皮癌 / MDSC / TAN / TAM / PD-1
Outline of Research at the Start

本研究では、PD-1免疫チェックポイント阻害剤の効果を左右する存在として、担癌宿主で増加する2種類のがん浸潤ミエロイド系細胞(マクロファージ系細胞と顆粒球系細胞)に着目している。それは、PD-1免疫チェックポイント阻害剤は、宿主の免疫抑制を標的とした治療であるが、先述した2種類のミエロイド系細胞に対して、どのように影響するかについては今もなお不明なためである。これらを明らかにすることで、効率的な複合免疫療法の開発に繋がるものと考えている。さらに、口腔癌臨床で使用可能な薬剤を考慮したPD-1免疫チェックポイント阻害併用療法についても検討したいと考えている。

Outline of Final Research Achievements

In the absence of T cells, myeloid lineage cells have been found to have no effect on cancer growth. T cells do not affect tumor growth in the absence of T cells. Furthermore, TRL3 agonists suppressed tumor growth by altering the properties of myeloid cells. We are currently exploring these phenomena. Clinically, the results showed an association between treatment response and neutrophil/lymphocyte ratio in patients treated with PD-1 immune checkpoint inhibitors.

Academic Significance and Societal Importance of the Research Achievements

免疫抑制性の骨髄系細胞はT細胞存在下でその抑制効果を示す可能性が示された。以上から、引き続き同抑制性細胞の制御あるいは性質変換(TLR3)についての研究を継続しつつT細胞のアップレギュレーション可能な試薬の探求を図ることは、担癌患者の治療選択肢に大きく影響すると考えている。臨床的には、PD-1免疫チェックポイント阻害剤投与患者の治療効果と好中球・リンパ球比との関連が示された。

Report

(4 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • 2019 Research-status Report
  • Research Products

    (24 results)

All 2021 2020 2019 2018

All Journal Article (10 results) (of which Int'l Joint Research: 7 results,  Peer Reviewed: 10 results,  Open Access: 8 results) Presentation (14 results)

  • [Journal Article] Neutrophil-to-Lymphocyte Ratio(NLR)as a Predictive Indicator of the Response to Nivolumab in Patients with Oral Squamous Cell Carcinoma2021

    • Author(s)
      Tachinami H, Tomihara K, Ikeda A, Sekido K, Sakurai K, Imaue S, Fujiwara K, Hayashi R, Noguchi M.
    • Journal Title

      Gan To Kagaku Ryoho.

      Volume: 48 Pages: 1485-1490

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Protumor role of estrogen receptor expression in oral squamous cell carcinoma cells2021

    • Author(s)
      Akyu Takei R, Tomihara K, Yamazaki M, Moniruzzaman R, Heshiki W, Sekido K, Tachinami H, Sakurai K, Yonesi A, Imaue S, Fujiwara K, Noguchi M.
    • Journal Title

      Oral Surg Oral Med Oral Pathol Oral Radiol.

      Volume: 132 Issue: 5 Pages: 549-565

    • DOI

      10.1016/j.oooo.2021.04.006

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Durable complete response to immunotherapy with anti-PD-1 antibody nivolumab in a patient with oral squamous cell carcinoma presenting with lung metastasis: A case report.2021

    • Author(s)
      Sekido K, Imaue, Tomihara K, Tachinami H, Yamagishi K, Okazawa S, Ikeda A, Fujiwara K, Noguchi M.
    • Journal Title

      Clin Case Rep.

      Volume: 9 Issue: 9

    • DOI

      10.1002/ccr3.4545

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Enhanced expression of PD-L1 in oral squamous cell carcinoma-derived CD11b + Gr-1 + cells and its contribution to immunosuppressive activity2020

    • Author(s)
      Fuse Hiroki、Tomihara Kei、Heshiki Wataru、Yamazaki Manabu、Akyu-Takei Rie、Tachinami Hidetake、Furukawa Ken-ichiro、Sakurai Kotaro、Rouwan Moniruzzaman、Noguchi Makoto
    • Journal Title

      Oral Oncology

      Volume: 59 Pages: 20-29

    • DOI

      10.1016/j.oraloncology.2016.05.012

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Orthotopic tongue squamous cell carcinoma (SCC) model exhibiting a different tumor-infiltrating T-cell status with margin-restricted CD8+ T cells and regulatory T cell-dominance, compared to skin SCC.2020

    • Author(s)
      Kashima Y, Nishii N, Tachinami H, Furusawa E, Nagai S, Harada H, Azuma M.
    • Journal Title

      Biochem Biophys Res Commun.

      Volume: 20 Issue: 1 Pages: 218-224

    • DOI

      10.1016/j.bbrc.2020.03.022

    • Related Report
      2020 Research-status Report 2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] CD36 expression on oral squamous cell carcinoma cells correlates with enhanced proliferation and migratory activity.2020

    • Author(s)
      Sakurai K, Tomihara K, Yamazaki M, Heshiki W, Moniruzzaman R, Sekido K, Tachinami H, Ikeda A, Imaue S, Fujiwara K, Noguchi M.
    • Journal Title

      Oral Dis.

      Volume: 0000 Issue: 4 Pages: 0000-0000

    • DOI

      10.1111/odi.13210

    • Related Report
      2020 Research-status Report 2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Differences of tumor-recruiting myeloid cells in murine squamous cell carcinoma influence the efficacy of immunotherapy combined with a TLR7 agonist and PD-L1 blockade2019

    • Author(s)
      Tachinami Hidetake、Nishii Naoto、Xia Yulong、Kashima Yoshihisa、Ohno Tatsukuni、Nagai Shigenori、Li Lixin、Lau Walter、Tomihara Kei、Noguchi Makoto、Azuma Miyuki
    • Journal Title

      Oral Oncology

      Volume: 91 Pages: 21-28

    • DOI

      10.1016/j.oraloncology.2019.02.014

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Endogenous IL-33 exerts CD8+ T cell antitumor responses overcoming pro-tumor effects by regulatory T cells in a colon carcinoma model.2019

    • Author(s)
      Xia Y, Ohno T, Nishii N, Bhingare A, Tachinami H, Kashima Y, Nagai S, Saito H, Nakae S, Azuma M.
    • Journal Title

      Biochem Biophys Res Commun.

      Volume: 2019 Issue: 2 Pages: 331-336

    • DOI

      10.1016/j.bbrc.2019.08.058

    • Related Report
      2020 Research-status Report 2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Alterations in composition of immune cells and impairment of anti-tumor immune response in aged oral cancer-bearing mice.2019

    • Author(s)
      Sekido K, Tomihara K, Tachinami H, Heshiki W, Sakurai K, Moniruzzaman R, Imaue S, Fujiwara K, Noguchi M.
    • Journal Title

      Oral Oncol.

      Volume: 99 Pages: 104462-104462

    • DOI

      10.1016/j.oraloncology.2019.104462

    • Related Report
      2020 Research-status Report 2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Systemic administration of a TLR7 agonist attenuates regulatory T cells by dendritic cell modification and overcomes resistance to PD-L1 blockade therapy.2018

    • Author(s)
      Nishii N, Tachinami H, Kondo Y, Xia Y, Kashima Y, Ohno T, Nagai S, Li L, Lau W, Harada H, Azuma M.
    • Journal Title

      Oncotarget

      Volume: 9 Issue: 17 Pages: 13301-13312

    • DOI

      10.18632/oncotarget.24327

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] 口腔癌に対するPAK4阻害による免疫学的修飾作用の解析.2021

    • Author(s)
      高塚団貴,冨原 圭,立浪秀剛,櫻井航太朗,高市真由,Yonesi Amirmoezz,野口 誠.
    • Organizer
      第75回日本口腔科学会学術集会
    • Related Report
      2021 Annual Research Report
  • [Presentation] Rapamycin induces phenotypic alterations of oral cancer cells that facilitate antitumor T cell response.2021

    • Author(s)
      Yonesi Amirmoezz,冨原 圭,高塚団貴,立浪秀剛,櫻井航太朗, 野口 誠.
    • Organizer
      第75回日本口腔科学会学術集会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 口腔癌切除後再建に用いた前腕皮弁に発生した扁平上皮癌の一例.2021

    • Author(s)
      津波古康太,池田篤司,今上修一,立浪秀剛,櫻井航太郎,高市真由,野口誠.
    • Organizer
      第46回日本口腔外科学会中部支部学術集会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 口腔癌に対するPAK4阻害による免疫学的修飾作用の解析.2021

    • Author(s)
      高塚団貴,冨原 圭,立浪秀剛,櫻井航太朗,高市真由,Yonesi Amirmoezz,野口 誠.
    • Organizer
      第66回日本口腔外科学会総会・学術大会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 口腔扁平上皮癌に対するニボルマブの効果と好中球/リンパ球比に関する研究.2021

    • Author(s)
      立浪 秀剛,冨原 圭,池田篤司,今上修一,岡本準也,中井裕美,黒原一人,宮﨑晃亘,新井直也,野口 誠.
    • Organizer
      第66回日本口腔外科学会総会・学術大会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 広範囲顎骨支持型装置を適用した症例の治療成績2020

    • Author(s)
      高塚団貴,立浪秀剛,津野宏彰,布施 浩樹,野口 誠
    • Organizer
      第39回日本口腔インプラント学会関東甲信越支部学術大会
    • Related Report
      2019 Research-status Report
  • [Presentation] 腫瘍に集積するミエロイド系細胞の違いはPD-L1阻害剤との併用免疫療法効果に影響を与える2019

    • Author(s)
      立浪秀剛,西井 直人,加島 義久,冨原 圭,野口 誠,東 みゆき
    • Organizer
      第73回日本口腔科学会学術集会
    • Related Report
      2019 Research-status Report
  • [Presentation] 骨吸収抑制薬関連顎骨壊死(ARONJ)に関する臨床的検討2019

    • Author(s)
      平識 亘,石戸克尚,立浪秀剛,朝倉みな実,冨原 圭,野口 誠
    • Organizer
      第62回日本口腔科学会中部地方部会学術集会
    • Related Report
      2019 Research-status Report
  • [Presentation] 老齢口腔癌マウスを用いた免疫細胞および抗腫瘍免疫応答に関する研究2019

    • Author(s)
      石戸克尚,立浪秀剛,櫻井航太郎,平識 亘,冨原 圭,野口 誠
    • Organizer
      第64回日本口腔外科学会総会・学術大会
    • Related Report
      2019 Research-status Report
  • [Presentation] 口腔癌におけるnivolumab投与による好中球数/リンパ球数比の変化2019

    • Author(s)
      立浪秀剛,冨原 圭,石戸克尚,池田篤司,藤原久美子,野口 誠
    • Organizer
      第64回日本口腔外科学会総会・学術大会
    • Related Report
      2019 Research-status Report
  • [Presentation] CT所見による下顎第三大臼歯抜歯後のオトガイ神経障害におけるハイリスク症例の検討2019

    • Author(s)
      高塚団貴,立浪秀剛,藤原久美子,仲盛健治,冨原圭,野口誠
    • Organizer
      第64回日本口腔外科学会総会・学術大会
    • Related Report
      2019 Research-status Report
  • [Presentation] 広範囲顎骨支持型装置を適用した症例の治療成績2019

    • Author(s)
      高塚団貴,立浪秀剛,今上修一,津野宏彰,石戸克尚,佐渡忠司,冨原圭,野口 誠
    • Organizer
      第23回公益社団法人日本顎顔面インプラント学会総会・学術大会,18th Annual meeting of Pan Pacific Implant Society (PPIS)
    • Related Report
      2019 Research-status Report
  • [Presentation] Differences of tumor-recruiting myeloid cells in murine squamous cell carcinoma influence the efficacy of immunotherapy combined with a TLR agonist and PD-L1 blockade2019

    • Author(s)
      Azuma M, Tachinami H, Nishii N, Xia Y, Kashima Y, Nagai S, Li L, Tomihara K, Noguchi M
    • Organizer
      17th Congress of the International Union of Immunological Societies (IUIS)
    • Related Report
      2019 Research-status Report
  • [Presentation] Neutrophil-to-lymphocyte ratio as a predictable biomarker for response to nivolumab in oral squamous cell carcinoma2019

    • Author(s)
      Tachinami H, Tomihara K, Noguchi M
    • Organizer
      The 78th J Annual Meeting of the Japanese Cancer Association
    • Related Report
      2019 Research-status Report

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Published: 2019-09-03   Modified: 2023-01-30  

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