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Immunological differece between pregnancy and cancer in terms of T cell receptor repertoire.

Research Project

Project/Area Number 19K18690
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 56040:Obstetrics and gynecology-related
Research InstitutionUniversity of Toyama

Principal Investigator

Tsuda Sayaka  富山大学, 学術研究部医学系, 助教 (60839075)

Project Period (FY) 2019-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2020: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2019: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywords細胞障害性T細胞 / 制御性T細胞 / T細胞受容体レパートリー / 流産 / 妊娠高血圧腎症 / 子宮体癌 / 妊娠 / 婦人科癌 / T細胞受容体
Outline of Research at the Start

胎児は母体にとって半異物(半分が自己で半分が他人)であるが免疫寛容が誘導されるため、拒絶されることなく妊娠が維持される。同様の免疫学的環境は、悪性腫瘍でも見られる。子宮局所における宿主(母体)の抗原特異的T細胞免疫の、妊娠と悪性腫瘍(子宮体癌)での相違を比較検討することで、習慣流産の治療法の開発ならびに婦人科悪性腫瘍に対する免疫療法の双方の領域に有用な知見が得られる。妊娠時・非妊娠時子宮内膜・子宮体癌で、制御性T細胞と細胞障害性T細胞のT細胞受容体のバリエーションとそれらの抗原特異性を比較検討し、生殖免疫学的に流早産、妊娠高血圧腎症の治療の糸口を見出し、腫瘍免疫学的に癌免疫療法の糸口を見出す。

Outline of Final Research Achievements

Feto-maternal tolerance and evasion of cancer from immune surveillance is similar in terms of T cell immunity. The objective of this study was to investigate difference of regulatory T cells(Treg) and cytotoxic T cells (CTLs) response between pregnancy and cancer by T cell receptor repertoire analysis.
In early pregnancy period, suppressing antigen-specific CTLs by non-specific Treg cells in the uterus was important. In late pregnancy, inhibition of antigen-specific CTLs and induction of antigen-specific tolerance by Treg cells in the uterus was important. In endometrial cancer, clonal expansion of CTLs were observed both in the uterus and peripheral blood. Furthermore, clonality of CTLs in peripheral blood reflected histology of cancer. On the other hand, either Treg cells and CTLs in peripheral blood did not significantly change between normal pregnancy and pregnancy complications. To study the local T cells , it is necessary to comprehend pathophysiology of pregnancy complications.

Academic Significance and Societal Importance of the Research Achievements

絨毛細胞(妊娠)と悪性腫瘍では免疫制御機構に類似点が多くある。宿主の抗原特異的T細胞免疫の、妊娠と悪性腫瘍(子宮体癌)での相違を比較検討することで、生殖免疫学的に流早産、妊娠高血圧腎症の治療の糸口を見出し、腫瘍免疫学的に癌免疫療法の糸口を見出すことを目的とした。
妊娠では制御性T細胞(Treg)と細胞障害性T細胞(CTL)の、子宮局所での抗原特異的T細胞免疫応答の変化を主体としており、末梢血には反映されないことから、局所に作用する免疫学的治療が望まれる。一方、子宮体癌では末梢血CTLクローンの多寡が腫瘍の性質を反映しており、免疫学的治療ならびにバイオマーカーとして応用できる可能性がある。

Report

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

    (17 results)

All 2021 2020 2019

All Journal Article (5 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 3 results,  Open Access: 2 results) Presentation (9 results) (of which Int'l Joint Research: 2 results,  Invited: 3 results) Book (3 results)

  • [Journal Article] The role of decidual regulatory T cells in the induction and maintenance of fetal antigen-specific tolerance: Imbalance between regulatory and cytotoxic T cells in pregnancy complications.2021

    • Author(s)
      Tsuda S, Nakashima A, Morita K, Shima T, Yoneda S, Kishi H, Saito S.
    • Journal Title

      Hum Immunol.

      Volume: S0198-8859 Issue: 5 Pages: 00040-9

    • DOI

      10.1016/j.humimm.2021.01.019

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Analysis of TCR repertoire and PD-1 expression in decidual and peripheral CD8+ T cells reveals distinct immune mechanisms in miscarriage and preeclampsia.2020

    • Author(s)
      Morita K, Tsuda S, Kobayashi E, Hamana H, Tsuda K, Shima T, Nakashima A, Ushijima A, Kishi H, Saito S.
    • Journal Title

      Front Immunol.

      Volume: 11 Pages: 1082-1082

    • DOI

      10.3389/fimmu.2020.01082

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Uterine CD11c+ cells induce the development of paternal antigen-specific Tregs via seminal plasma priming2020

    • Author(s)
      Shima Tomoko、Nakashima Akitoshi、Yasuda Ippei、Ushijima Akemi、Inada Kumiko、Tsuda Sayaka、Yoshino Osamu、Tomura Michio、Saito Shigeru
    • Journal Title

      Journal of Reproductive Immunology

      Volume: - Pages: 103165-103165

    • DOI

      10.1016/j.jri.2020.103165

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] 母子感染症の必修知識-エキスパートに学び予防につなげる 妊婦の免疫学的特徴.2020

    • Author(s)
      森田恵子, 津田さやか, 齋藤滋
    • Journal Title

      小児内科

      Volume: 52 Pages: 8-13

    • Related Report
      2020 Annual Research Report
  • [Journal Article] 妊娠高血圧症候群update 病態 制御性T細胞(Treg)2019

    • Author(s)
      津田さやか,齋藤滋
    • Journal Title

      周産期医学

      Volume: 49 Pages: 1334-1339

    • Related Report
      2019 Research-status Report
  • [Presentation] 母児の予後からみた自己免疫性疾患罹患女性への妊娠支援~全国実態調査と富山大学における試み~.2020

    • Author(s)
      津田さやか
    • Organizer
      第38回周産期学シンポジウム
    • Related Report
      2020 Annual Research Report
  • [Presentation] 抗結核薬治療で無月経が改善した性器結核の一例.2020

    • Author(s)
      津田さやか,竹村京子,伊東雅美,森田恵子,安田一平,島田なつみ,荒木左諭,島友子,山本善裕,中島彰俊
    • Organizer
      第11回日本性感染症学会北陸支部学術講演会
    • Related Report
      2020 Annual Research Report
  • [Presentation] WoCBA患者さんのためのリウマチ科と産科の連携とは?「リウマチ・膠原病科と産科・婦人科の連携~ベストプラクティスの事例を中心に~」2020

    • Author(s)
      津田さやか
    • Organizer
      Interaction in Clinical Intelligence in 神奈川
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] 母子間免疫寛容の維持に制御性T細胞が果たす役割.2020

    • Author(s)
      津田さやか
    • Organizer
      第13回 母児間免疫病研究会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] 産婦人科医が診るWoCBA(Women of Child-Bearing Age)RA患者の現状と課題.2020

    • Author(s)
      津田さやか
    • Organizer
      第35回日本臨床リウマチ学会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] Single-cell T cell receptor (TCR) repertoire analysis revealed insufficient clonal expansion of decidual effector regulatory T cells was present in preeclampsia, but not in miscarriage, in humans.2019

    • Author(s)
      Sayaka Tsuda, Keiko Morita, Tomoko Shima, Akemi Ushijima, Kei Tsuda, Shigeru Saito
    • Organizer
      第71回日本産科婦人科学会学術講演会
    • Related Report
      2019 Research-status Report
  • [Presentation] Failure of clonal expansion of decidual regulatory T cells is present in preeclampsia, but not in miscarriage, suggesting that fetal antigen - specific tolerance might be disturbed in preeclampsia.2019

    • Author(s)
      Sayaka Tsuda, Hiroshi Hamana, Tomoko Shima, Akemi Ushijima, Kei Tsuda, Atsushi Muraguchi, Hiroyuki Kishi and Shigeru Saito
    • Organizer
      14th World Congress of the International Society for Immunology of Reproduction. The 34th Annual Meeting of the Japanese Society for Immunology of Reproduction
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Clonally expanded populations of cytotoxic T cell in tumor infiltrated lymphocyte and peripheral blood in uterine endometrial cancer2019

    • Author(s)
      Kei Tsuda, Akitoshi Nakashima, Sayaka Tsuda, Tomoko Shima, Osamu Yoshino, Shigeru Saito
    • Organizer
      第71回日本産科婦人科学会学術講演会
    • Related Report
      2019 Research-status Report
  • [Presentation] Commom TCRβ Repertoire was found in both decidual and peripheral CD8+T cells in normal pregnancy2019

    • Author(s)
      Keiko Morita, Eiji Kobayashi, Sayaka Tsuda, Kiyomi Shitaoka, Tatsuhiko Ozawa, Hiroshi Hamana, Shigeru Saito, Hiroyuki Kishi
    • Organizer
      第48回日本免疫学会
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Book] 産婦人科臨床シリーズ 3分娩・産褥期の正常と異常/周産期感染症2021

    • Author(s)
      津田さやか, 中島彰俊, 齋藤滋
    • Total Pages
      381
    • Publisher
      中山書店
    • ISBN
      9784521747637
    • Related Report
      2020 Annual Research Report
  • [Book] Reproductive Immunology Basic Concepts volume12021

    • Author(s)
      Tsuda S, Saito S
    • Total Pages
      445
    • Publisher
      Academic Press
    • ISBN
      9780128185087
    • Related Report
      2020 Annual Research Report
  • [Book] 不育症2020

    • Author(s)
      齋藤 滋, 津田さやか
    • Total Pages
      248
    • Publisher
      メジカルビュー社
    • ISBN
      9784758319966
    • Related Report
      2020 Annual Research Report

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Published: 2019-04-18   Modified: 2022-01-27  

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