論文

査読有り
2012年10月

Absence of LTB4/BLT1 axis facilitates generation of mouse GM-CSF-induced long-lasting antitumor immunologic memory by enhancing innate and adaptive immune systems

BLOOD
  • Yosuke Yokota
  • ,
  • Hiroyuki Inoue
  • ,
  • Yumiko Matsumura
  • ,
  • Haruka Nabeta
  • ,
  • Megumi Narusawa
  • ,
  • Ayumi Watanabe
  • ,
  • Chika Sakamoto
  • ,
  • Yasuki Hijikata
  • ,
  • Mutsunori Iga-Murahashi
  • ,
  • Koichi Takayama
  • ,
  • Fumiyuki Sasaki
  • ,
  • Yoichi Nakanishi
  • ,
  • Takehiko Yokomizo
  • ,
  • Kenzaburo Tani

120
17
開始ページ
3444
終了ページ
3454
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1182/blood-2011-10-383240
出版者・発行元
AMER SOC HEMATOLOGY

BLT1 is a high-affinity receptor for leukotriene B4 (LTB4) that is a potent lipid chemoattractant for myeloid leukocytes. The role of LTB4/BLT1 axis in tumor immunology, including cytokine-based tumor vaccine, however, remains unknown. We here demonstrated that BLT1-deficient mice rejected subcutaneous tumor challenge of GM-CSF gene-transduced WEHI3B (WGM) leukemia cells (KO/WGM) and elicited robust antitumor responses against second tumor challenge with WEHI3B cells. During GM-CSF-induced tumor regression, the defective LTB4/BLT1 signaling significantly reduced tumor-infiltrating myeloid-derived suppressor cells, increased the maturation status of dendritic cells in tumor tissues, enhanced their CD4(+) T-cell stimulation capacity and migration rate of dendritic cells that had phagocytosed tumor-associated antigens into tumor-draining lymph nodes, suggesting a positive impact on GM-CSF-sensitized innate immunity. Furthermore, KO/WGM mice displayed activated adaptive immunity by attenuating regulatory CD4(+) T subsets and increasing numbers of Th17 and memory CD44(hi)CD4(+) T subsets, both of which elicited superior antitumor effects as evidenced by adoptive cell transfer. In vivo depletion assays also revealed that CD4(+) T cells were the main effectors of the persistent antitumor immunity. Our data collectively underscore a negative role of LTB4/BLT1 signaling in effective generation and maintenance of GM-CSF-induced antitumor memory CD4(+) T cells. (Blood. 2012;120(17):3444-3454)

Web of Science ® 被引用回数 : 15

リンク情報
DOI
https://doi.org/10.1182/blood-2011-10-383240
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/22936657
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000311623800011&DestApp=WOS_CPL

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