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

Nat Commun. 2022 Oct 19;13(1):6203. doi: 10.1038/s41467-022-33968-5.

Bihui Cao ^# ¹ ², Manting Liu ^# ¹ ², Lu Wang ², Kangshun Zhu ¹, Mingyue Cai ¹, Xiaopei Chen ², Yunfei Feng ², Shuo Yang ³ ⁴, Shengyu Fu ³, Cheng Zhi ⁵, Xiaodie Ye ², Jian Zhang ², Zhiru Zhang ², Xin Yang ⁶, Ming Zhao ⁷, Qingde Wu ⁸, Linfeng Xu ⁹, Lili Yang ¹⁰, Hui Lian ¹, Qi Zhao ¹¹, Zhenfeng Zhang ¹² ¹³

Affiliations

1 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.
11 Institute of Translational Medicine, Cancer Centre, Faculty of Health Sciences, University of Macau, Macau SAR, 999078, China. [email protected].
12 Department of Minimally Invasive Interventional Radiology, the Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510260, China. [email protected].
13 Central Laboratory, the Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510260, China. [email protected].
# Contributed equally.

PMID: 36261437 DOI: 10.1038/s41467-022-33968-5

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.

Name
Email *

	Sorry, but the email address you supplied was invalid.