Depletion of central memory CD8+ T cells might impede the antitumor therapeutic effect of Mogamulizumab

Yuka Maeda, Hisashi Wada, Daisuke Sugiyama, Takuro Saito, Takuma Irie, Kota Itahashi, Kodai Minoura, Susumu Suzuki, Takashi Kojima, Kazuhiro Kakimi, Jun Nakajima, Takeru Funakoshi, Shinsuke Iida, Mikio Oka, Teppei Shimamura, Toshihiko Doi, Yuichiro Doki, Eiichi Nakayama, Ryuzo Ueda, Hiroyoshi Nishikawa

研究成果: Article査読

抄録

Regulatory T (Treg) cells are important negative regulators of immune homeostasis, but in cancers they tone down the anti-tumor immune response. They are distinguished by high expression levels of the chemokine receptor CCR4, hence their targeting by the anti-CCR4 monoclonal antibody mogamulizumab holds therapeutic promise. Here we show that despite a significant reduction in peripheral effector Treg cells, clinical responses are minimal in a cohort of patients with advanced CCR4-negative solid cancer in a phase Ib study (NCT01929486). Comprehensive immune-monitoring reveals that the abundance of CCR4-expressing central memory CD8+ T cells that are known to play roles in the antitumor immune response is reduced. In long survivors, characterised by lower CCR4 expression in their central memory CD8+ T cells possessed and/or NK cells with an exhausted phenotype, cell numbers are eventually maintained. Our study thus shows that mogamulizumab doses that are currently administered to patients in clinical studies may not differentiate between targeting effector Treg cells and central memory CD8+ T cells, and dosage refinement might be necessary to avoid depletion of effector components during immune therapy.

本文言語English
論文番号7280
ジャーナルNature communications
12
1
DOI
出版ステータスPublished - 2021 12月

ASJC Scopus subject areas

  • 化学 (全般)
  • 生化学、遺伝学、分子生物学(全般)
  • 物理学および天文学(全般)

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