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CD36-mediated metabolic crosstalk between tumor cells and macrophages affects liver metastasis

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Listed:
  • Ping Yang

    (Chongqing Medical University)

  • Hong Qin

    (Chongqing Medical University)

  • Yiyu Li

    (Chongqing Medical University)

  • Anhua Xiao

    (Chongqing Medical University)

  • Enze Zheng

    (Chongqing Medical University)

  • Han Zeng

    (Chongqing Medical University)

  • Chunxiao Su

    (Chongqing Medical University)

  • Xiaoqing Luo

    (Chongqing Medical University)

  • Qiannan Lu

    (Chongqing Medical University)

  • Meng Liao

    (Chongqing Medical University)

  • Lei Zhao

    (Chongqing Medical University)

  • Li Wei

    (Chongqing Medical University)

  • Zac Varghese

    (University College London Medical School, Royal Free Campus, University College London)

  • John F. Moorhead

    (University College London Medical School, Royal Free Campus, University College London)

  • Yaxi Chen

    (Chongqing Medical University)

  • Xiong Z. Ruan

    (Chongqing Medical University
    University College London Medical School, Royal Free Campus, University College London)

Abstract

Liver metastasis is highly aggressive and treatment-refractory, partly due to macrophage-mediated immune suppression. Understanding the mechanisms leading to functional reprogramming of macrophages in the tumor microenvironment (TME) will benefit cancer immunotherapy. Herein, we find that the scavenger receptor CD36 is upregulated in metastasis-associated macrophages (MAMs) and deletion of CD36 in MAMs attenuates liver metastasis in mice. MAMs contain more lipid droplets and have the unique capability in engulfing tumor cell-derived long-chain fatty acids, which are carried by extracellular vesicles. The lipid-enriched vesicles are preferentially partitioned into macrophages via CD36, that fuel macrophages and trigger their tumor-promoting activities. In patients with liver metastases, high expression of CD36 correlates with protumoral M2-type MAMs infiltration, creating a highly immunosuppressive TME. Collectively, our findings uncover a mechanism by which tumor cells metabolically interact with macrophages in TME, and suggest a therapeutic potential of targeting CD36 as immunotherapy for liver metastasis.

Suggested Citation

  • Ping Yang & Hong Qin & Yiyu Li & Anhua Xiao & Enze Zheng & Han Zeng & Chunxiao Su & Xiaoqing Luo & Qiannan Lu & Meng Liao & Lei Zhao & Li Wei & Zac Varghese & John F. Moorhead & Yaxi Chen & Xiong Z. R, 2022. "CD36-mediated metabolic crosstalk between tumor cells and macrophages affects liver metastasis," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-33349-y
    DOI: 10.1038/s41467-022-33349-y
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