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Motility and tumor infiltration are key aspects of invariant natural killer T cell anti-tumor function

Author

Listed:
  • Chenxi Tian

    (University of Science and Technology of China)

  • Yu Wang

    (University of Science and Technology of China)

  • Miya Su

    (University of Science and Technology of China)

  • Yuanyuan Huang

    (University of Science and Technology of China)

  • Yuwei Zhang

    (University of Science and Technology of China)

  • Jiaxiang Dou

    (Hefei Comprehensive National Science Center)

  • Changfeng Zhao

    (University of Science and Technology of China)

  • Yuting Cai

    (University of Science and Technology of China)

  • Jun Pan

    (University of Science and Technology of China)

  • Shiyu Bai

    (University of Science and Technology of China)

  • Qielan Wu

    (University of Science and Technology of China)

  • Sanwei Chen

    (The First Affiliated Hospital of Anhui Medical University)

  • Shuhang Li

    (University of Science and Technology of China)

  • Di Xie

    (University of Science and Technology of China)

  • Rong Lv

    (Anhui Blood Center)

  • Yusheng Chen

    (Hefei Comprehensive National Science Center)

  • Yucai Wang

    (University of Science and Technology of China
    University of Science and Technology of China)

  • Sicheng Fu

    (University of Science and Technology of China)

  • Huimin Zhang

    (University of Science and Technology of China)

  • Li Bai

    (University of Science and Technology of China
    Hefei Comprehensive National Science Center
    University of Science and Technology of China
    University of Science and Technology of China)

Abstract

Dysfunction of invariant natural killer T (iNKT) cells contributes to immune resistance of tumors. Most mechanistic studies focus on their static functional status before or after activation, not considering motility as an important characteristic for antigen scanning and thus anti-tumor capability. Here we show via intravital imaging, that impaired motility of iNKT cells and their exclusion from tumors both contribute to the diminished anti-tumor iNKT cell response. Mechanistically, CD1d, expressed on macrophages, interferes with tumor infiltration of iNKT cells and iNKT-DC interactions but does not influence their intratumoral motility. VCAM1, expressed by cancer cells, restricts iNKT cell motility and inhibits their antigen scanning and activation by DCs via reducing CDC42 expression. Blocking VCAM1-CD49d signaling improves motility and activation of intratumoral iNKT cells, and consequently augments their anti-tumor function. Interference with macrophage-iNKT cell interactions further enhances the anti-tumor capability of iNKT cells. Thus, our findings provide a direction to enhance the efficacy of iNKT cell-based immunotherapy via motility regulation.

Suggested Citation

  • Chenxi Tian & Yu Wang & Miya Su & Yuanyuan Huang & Yuwei Zhang & Jiaxiang Dou & Changfeng Zhao & Yuting Cai & Jun Pan & Shiyu Bai & Qielan Wu & Sanwei Chen & Shuhang Li & Di Xie & Rong Lv & Yusheng Ch, 2024. "Motility and tumor infiltration are key aspects of invariant natural killer T cell anti-tumor function," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-45208-z
    DOI: 10.1038/s41467-024-45208-z
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    References listed on IDEAS

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    1. Laura Codarri Deak & Valeria Nicolini & Masao Hashimoto & Maria Karagianni & Petra C. Schwalie & Laura Lauener & Eleni Maria Varypataki & Marine Richard & Esther Bommer & Johannes Sam & Stefanie Jolle, 2022. "PD-1-cis IL-2R agonism yields better effectors from stem-like CD8+ T cells," Nature, Nature, vol. 610(7930), pages 161-172, October.
    2. Xue Bai & Ze-Qin Guo & Yan-Pei Zhang & Zhen-zhen Fan & Li-Juan Liu & Li Liu & Li-Li Long & Si-Cong Ma & Jian Wang & Yuan Fang & Xin-Ran Tang & Yu-Jie Zeng & Xinghua Pan & De-Hua Wu & Zhong-Yi Dong, 2023. "CDK4/6 inhibition triggers ICAM1-driven immune response and sensitizes LKB1 mutant lung cancer to immunotherapy," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    3. Sicheng Fu & Kaixin He & Chenxi Tian & Hua Sun & Chenwen Zhu & Shiyu Bai & Jiwei Liu & Qielan Wu & Di Xie & Ting Yue & Zhuxia Shen & Qingqing Dai & Xiaojun Yu & Shu Zhu & Gang Liu & Rongbin Zhou & She, 2020. "Impaired lipid biosynthesis hinders anti-tumor efficacy of intratumoral iNKT cells," Nature Communications, Nature, vol. 11(1), pages 1-15, December.
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