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Remodelling of tumour microenvironment by microwave ablation potentiates immunotherapy of AXL-specific CAR T cells against non-small cell lung cancer

Author

Listed:
  • Bihui Cao

    (the Second Affiliated Hospital of Guangzhou Medical University
    the Second Affiliated Hospital of Guangzhou Medical University)

  • Manting Liu

    (the Second Affiliated Hospital of Guangzhou Medical University
    the Second Affiliated Hospital of Guangzhou Medical University)

  • Lu Wang

    (the Second Affiliated Hospital of Guangzhou Medical University)

  • Kangshun Zhu

    (the Second Affiliated Hospital of Guangzhou Medical University)

  • Mingyue Cai

    (the Second Affiliated Hospital of Guangzhou Medical University)

  • Xiaopei Chen

    (the Second Affiliated Hospital of Guangzhou Medical University)

  • Yunfei Feng

    (the Second Affiliated Hospital of Guangzhou Medical University)

  • Shuo Yang

    (University of Macau
    Guangzhou Medical University)

  • Shengyu Fu

    (University of Macau)

  • Cheng Zhi

    (the Second Affiliated Hospital of Guangzhou Medical University)

  • Xiaodie Ye

    (the Second Affiliated Hospital of Guangzhou Medical University)

  • Jian Zhang

    (the Second Affiliated Hospital of Guangzhou Medical University)

  • Zhiru Zhang

    (the Second Affiliated Hospital of Guangzhou Medical University)

  • Xin Yang

    (the Second Affiliated Hospital of Guangzhou Medical University)

  • Ming Zhao

    (Cancer Center, Sun Yat-sen University)

  • Qingde Wu

    (Shunde Chinese Medicine Hospital, the Affiliated Hospital of Traditional Chinese Medicine University of Guangzhou)

  • Linfeng Xu

    (Sun Yat-sen University)

  • Lili Yang

    (Sun Yat-sen University)

  • Hui Lian

    (the Second Affiliated Hospital of Guangzhou Medical University)

  • Qi Zhao

    (University of Macau)

  • Zhenfeng Zhang

    (the Second Affiliated Hospital of Guangzhou Medical University
    the Second Affiliated Hospital of Guangzhou Medical University)

Abstract

The complex immunosuppressive tumour microenvironment (TME) and lack of tumour-specific targets hinder the application of chimeric antigen receptor (CAR) T cells in the treatment of solid tumours. Combining local treatment with CAR T cell immunotherapy may regulate the TME and enhance the killing potency of CAR T cells in solid tumours. Here, we show that AXL, which is highly expressed in non-small cell lung cancer (NSCLC) but not in normal tissues, might be a target for CAR T cell therapy. AXL-CAR T cells alone cause moderate tumour regression in subcutaneous and pulmonary metastatic lung cancer cell-derived xenograft models. Combination of microwave ablation (MWA) and AXL-CAR T cells have superior antitumour efficacy. MWA enhances the activation, infiltration, persistence and tumour suppressive properties of AXL-CAR T cells in AXL-positive NSCLC patient-derived xenograft tumours via TME remodelling. The combination therapy increases the mitochondrial oxidative metabolism of tumour-infiltrating CAR T cells. Combination treatment induces significant tumour suppression without observed toxicities in humanized immunocompetent mice. The synergistic therapeutic effect of MWA and AXL-CAR T cells may be valuable for NSCLC treatment.

Suggested Citation

  • Bihui Cao & Manting Liu & Lu Wang & Kangshun Zhu & Mingyue Cai & Xiaopei Chen & Yunfei Feng & Shuo Yang & Shengyu Fu & Cheng Zhi & Xiaodie Ye & Jian Zhang & Zhiru Zhang & Xin Yang & Ming Zhao & Qingde, 2022. "Remodelling of tumour microenvironment by microwave ablation potentiates immunotherapy of AXL-specific CAR T cells against non-small cell lung cancer," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
  • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-33968-5
    DOI: 10.1038/s41467-022-33968-5
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    References listed on IDEAS

    as
    1. Yao Wang & Chuan Tong & Hanren Dai & Zhiqiang Wu & Xiao Han & Yelei Guo & Deyun Chen & Jianshu Wei & Dongdong Ti & Zongzhi Liu & Qian Mei & Xiang Li & Liang Dong & Jing Nie & Yajing Zhang & Weidong Ha, 2021. "Low-dose decitabine priming endows CAR T cells with enhanced and persistent antitumour potential via epigenetic reprogramming," Nature Communications, Nature, vol. 12(1), pages 1-18, December.
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    Cited by:

    1. Xinyu Tang & Xinrui Mao & Peiwen Ling & Muxin Yu & Hua Pan & Jiaming Wang & Mingduo Liu & Hong Pan & Wen Qiu & Nan Che & Kai Zhang & Feifan Bao & Hongwei Peng & Qiang Ding & Shui Wang & Wenbin Zhou, 2024. "Glycolysis inhibition induces anti-tumor central memory CD8+T cell differentiation upon combination with microwave ablation therapy," Nature Communications, Nature, vol. 15(1), pages 1-20, December.

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