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

2020 Fiscal Year Final Research Report

• Project/Area Number: 19K18690
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 56040:Obstetrics and gynecology-related
• Research Institution: University 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
• 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

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.

Free Research Field

産科婦人科

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。