論文

国際誌
2021年10月17日

PD-1 blockade therapy augments the antitumor effects of lymphodepletion and adoptive T cell transfer.

Cancer immunology, immunotherapy : CII
  • Miho Takahashi
  • Satoshi Watanabe
  • Ryo Suzuki
  • Masashi Arita
  • Ko Sato
  • Miyuki Sato
  • Yuki Sekiya
  • Yuko Abe
  • Toshiya Fujisaki
  • Aya Ohtsubo
  • Satoshi Shoji
  • Koichiro Nozaki
  • Kosuke Ichikawa
  • Rie Kondo
  • Yu Saida
  • Satoshi Hokari
  • Nobumasa Aoki
  • Masachika Hayashi
  • Yasuyoshi Ohshima
  • Toshiyuki Koya
  • Toshiaki Kikuchi
  • 全て表示

記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1007/s00262-021-03078-0

Lymphodepleting cytotoxic regimens enhance the antitumor effects of adoptively transferred effector and naïve T cells. Although the mechanisms of antitumor immunity augmentation by lymphodepletion have been intensively investigated, the effects of lymphodepletion followed by T cell transfer on immune checkpoints in the tumor microenvironment remain unclear. The current study demonstrated that the expression of immune checkpoint molecules on transferred donor CD4+ and CD8+ T cells was significantly decreased in lymphodepleted tumor-bearing mice. In contrast, lymphodepletion did not reduce immune checkpoint molecule levels on recipient CD4+ and CD8+ T cells. Administration of anti-PD-1 antibodies after lymphodepletion and adoptive transfer of T cells significantly inhibited tumor progression. Further analysis revealed that transfer of both donor CD4+ and CD8+ T cells was responsible for the antitumor effects of a combination therapy consisting of lymphodepletion, T cell transfer and anti-PD-1 treatment. Our findings indicate that a possible mechanism underlying the antitumor effects of lymphodepletion followed by T cell transfer is the prevention of donor T cell exhaustion and dysfunction. PD-1 blockade may reinvigorate exhausted recipient T cells and augment the antitumor effects of lymphodepletion and adoptive T cell transfer.

リンク情報
DOI
https://doi.org/10.1007/s00262-021-03078-0
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/34657194
ID情報
  • DOI : 10.1007/s00262-021-03078-0
  • PubMed ID : 34657194

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