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2021 Fiscal Year Final Research Report

Contribution of LFA-1 integrin in T cell trogocytosis

Research Project

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Project/Area Number 19K07634
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 50010:Tumor biology-related
Research InstitutionTohoku University

Principal Investigator

Koyu Ito  東北大学, 加齢医学研究所, 助教 (90609497)

Project Period (FY) 2019-04-01 – 2022-03-31
Keywordsトロゴサイトーシス / インテグリン / 癌
Outline of Final Research Achievements

In this study, we investigated the role of LFA-1 in trogocytosis on T cell. When T cells were stimulated with antigen, T cell trogocytosis was enhanced and LFA-1 blocking antibody inhibited antigen-dependent trogocytosis. In addition, integrin activation by cross-linking of CD98 resulted in the enhancement of trogocytosis. These data indicated that LFA-1 activation is involved in T cell trogocytosis. Next, to examine the contribution of trogocytosis in cancer, mice were injected with B16F10 melanoma cells. we found that CD98 expression was increased in tumor infiltrating CD8 T cell, and that these cells acquired CD80 and CD86 molecule by trogocytosis. These “trogocytosed” T cells suppressed activation of another T cell. Cancer progression was suppressed by inhibition of trogocytosis. These data suggested that T cell trogocytosis contributed to generate immune suppressive environment in cancer, and that this event has potential to be novel target in cancer immunotherapy.

Free Research Field

免疫学

Academic Significance and Societal Importance of the Research Achievements

トロゴサイトーシスは細胞間接着を介して比較的容易に誘導することができ、その制御によって病態に応じた新規機能を免疫細胞に付与できると考えられる。本研究ではTCR刺激によるLFA-1活性化はトロゴサイトーシスに寄与すること、CD98抗体はトロゴサイトーシスを亢進させることを明らかにした。さらに、癌微小環境においてはトロゴサイトーシスを介して免疫抑制細胞が形成されることを明らかにし、これを阻害することによって癌の進展が抑制されることを明らかにした。この結果は、トロゴサイトーシスの制御が癌免疫療法の新規標的になる可能性を示唆している。

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Published: 2023-01-30  

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