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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
Cao, Bihui1,2; Liu, Manting1,2; Wang, Lu2; Zhu, Kangshun1; Cai, Mingyue1; Chen, Xiaopei2; Feng, Yunfei2; Yang, Shuo3,4; Fu, Shengyu3; Zhi, Cheng5; Ye, Xiaodie2; Zhang, Jian2; Zhang, Zhiru2; Yang, Xin6; Zhao, Ming7; Wu, Qingde8; Xu, Linfeng9; Yang, Lili10; Lian, Hui1; Zhao, Qi3; Zhang, Zhenfeng1,2
2022-10-19
Source PublicationNature Communications
ISSN2041-1723
Volume13Issue:1Pages:6203
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.

KeywordGrowth Antibody Thermal Ablation Receptor Tyrosine Kinases
DOI10.1038/s41467-022-33968-5
URLView the original
Indexed BySCIE
Language英語English
WOS Research AreaScience & Technology - Other Topics
WOS SubjectMultidisciplinary Sciences
WOS IDWOS:000870431200016
PublisherNATURE PORTFOLIO, HEIDELBERGER PLATZ 3, BERLIN 14197, GERMANY
Scopus ID2-s2.0-85140255190
Fulltext Access
Citation statistics
Document TypeJournal article
CollectionFaculty of Health Sciences
DEPARTMENT OF BIOMEDICAL SCIENCES
Corresponding AuthorZhao, Qi; Zhang, Zhenfeng
Affiliation1.Department of Minimally Invasive Interventional Radiology, the Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510260, China
2.Central Laboratory, the Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510260, China
3.Institute of Translational Medicine, Cancer Centre, Faculty of Health Sciences, University of Macau, Macau SAR 999078, China
4.Faculty of Pharmacy, Guangzhou Medical University, Guangzhou, 511436, China
5.Department of Pathology, the Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510260, China
6.Department of Thoracic Surgery, the Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510260, China
7.Department of Interventional Radiology, Cancer Center, Sun Yat-sen University, Guangzhou, 510060, China
8.Department of Radiology, Shunde Chinese Medicine Hospital, the Affiliated Hospital of Traditional Chinese Medicine University of Guangzhou, Foshan, 528000, China
9.Department of Interventional Therapy, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, 510120, China
10.Department of Nutrition, School of Public Health, Sun Yat-sen University, Guangzhou, 510080, China
Corresponding Author AffilicationCancer Centre
Recommended Citation
GB/T 7714
Cao, Bihui,Liu, Manting,Wang, Lu,et al. Remodelling of tumour microenvironment by microwave ablation potentiates immunotherapy of AXL-specific CAR T cells against non-small cell lung cancer[J]. Nature Communications, 2022, 13(1), 6203.
APA Cao, Bihui., Liu, Manting., Wang, Lu., Zhu, Kangshun., Cai, Mingyue., Chen, Xiaopei., Feng, Yunfei., Yang, Shuo., Fu, Shengyu., Zhi, Cheng., Ye, Xiaodie., Zhang, Jian., Zhang, Zhiru., Yang, Xin., Zhao, Ming., Wu, Qingde., Xu, Linfeng., Yang, Lili., Lian, Hui., ...& Zhang, Zhenfeng (2022). Remodelling of tumour microenvironment by microwave ablation potentiates immunotherapy of AXL-specific CAR T cells against non-small cell lung cancer. Nature Communications, 13(1), 6203.
MLA Cao, Bihui,et al."Remodelling of tumour microenvironment by microwave ablation potentiates immunotherapy of AXL-specific CAR T cells against non-small cell lung cancer".Nature Communications 13.1(2022):6203.
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