2024-03-28T12:19:16Z
https://niigata-u.repo.nii.ac.jp/oai
oai:niigata-u.repo.nii.ac.jp:00005644
2022-12-15T03:38:46Z
453:455
471:561:562
抗癌剤を用いたリンパ球除去後の抗腫瘍免疫における、抗癌剤耐性エフェクターおよび制御性T cellsの重要な役割
Critical Roles of Chemoresistant Effector and Regulatory T Cells in Antitumor Immunity after Lymphodepleting Chemotherapy
Critical Roles of Chemoresistant Effector and Regulatory T Cells in Antitumor Immunity after Lymphodepleting Chemotherapy
Saida, Yu
50651
新潟大学
博士(医学)
Antitumor immunity is augmented by cytotoxic lymphodepletion therapies. Adoptively transferred naive and effector T cells proliferate extensively and show enhanced antitumor effects in lymphopenic recipients. Although the impact of lymphodepletion on transferred donor T cells has been well evaluated, its influence on recipient T cells is largely unknown. The current study demonstrates that both regulatory T cells (Tregs) and effector CD8^+ T cells from lymphopenic recipients play critical roles in the development of antitumor immunity after lymphodepletion. Cyclophosphamide (CPA) treatment depleted lymphocytes more efficiently than other cytotoxic agents; however, the percentage of CD4^+CD25^+ Forkhead box P3^+ Tregs was significantly increased in CPA-treated lymphopenic mice. Depletion of these chemoresistant Tregs following CPA treatment and transfer of naive CD4^+ T cells augmented the antitumor immunity and significantly suppressed tumor progression. Further analyses revealed that recipient CD8^+ T cells were responsible for this augmentation. Using Rag2^<-/-> mice or depletion of recipient CD8^+ T cells after CPA treatment abrogated the augmentation of antitumor effects in CPA-treated reconstituted mice. The transfer of donor CD4^+ T cells enhanced the proliferation of CD8^+ T cells and the priming of tumor-specific CD8^+ T cells originating from the lymphopenic recipients. These results highlight the importance of the recipient cells surviving cytotoxic regimens in cancer immunotherapies.
学位の種類: 博士(医学). 報告番号: 甲第4064号. 学位記番号: 新大院博(医)甲第653号. 学位授与年月日: 平成27年9月24日
The Journal of Immunology. 2015, 195(2), 726-735.
新大院博(医)甲第653号
thesis
新潟大学
2015-09-24
2015-09-24
application/pdf
application/pdf
13101甲第4064号
https://niigata-u.repo.nii.ac.jp/record/5644/files/h27nmk653.pdf
https://niigata-u.repo.nii.ac.jp/record/5644/files/h27nmk653_a.pdf
eng
info:doi/10.4049/jimmunol.1401468