Grain‐sized moxibustion promotes NK cell antitumour immunity by inhibiting adrenergic signalling in non–small cell lung cancer

• Published in: Journal of cellular and molecular medicine 2021-03, Vol.25 (6), p.2900-2908
• Main Authors: Hu, Dan, Shen, Weiming, Gong, Chenyuan, Fang, Cheng, Yao, Chao, Zhu, Xiaowen, Wang, Lixin, Zhao, Chen, Zhu, Shiguo
• Format: Article
• Language: English
• Subjects: Acupuncture; Adrenergic receptors; adrenergic signalling; antitumour immunity; Apoptosis; Cancer immunotherapy; Cancer therapies; CD4 antigen; CD8 antigen; Cell activation; Cytotoxicity; Epinephrine; Flow cytometry; Gene expression; Immunity; Immunotherapy; Lung cancer; Lymphocytes; Lymphocytes T; Metastases; moxibustion; Natural killer cells; NK cells; Non-small cell lung carcinoma; non–small cell lung cancer; Original; Phenotypes; Propranolol; Ribonucleic acid; RNA; Small cell lung carcinoma; Software; Tumors; Variance analysis; Xenografts
• ISSN: 1582-1838; 1582-4934
• DOI: 10.1111/jcmm.16320

Lung cancer is the leading cause of cancer‐related death worldwide, and non–small cell lung cancer (NSCLC) accounts for 85% of lung cancer diagnoses. As an ancient therapy, moxibustion has been used to treat cancer‐related symptoms in clinical practice. However, its antitumour effect on NSCLC remains largely unexplored. In the present study, a Lewis lung cancer (LLC) xenograft tumour model was established, and grain‐sized moxibustion (gMoxi) was performed at the acupoint of Zusanli (ST36). Flow cytometry and RNA sequencing (RNA‐Seq) were used to access the immune cell phenotype, cytotoxicity and gene expression. PK136, propranolol and epinephrine were used for natural killer (NK) cell depletion, β‐adrenoceptor blockade and activation, respectively. Results showed that gMoxi significantly inhibited LLC tumour growth. Moreover, gMoxi significantly increased the proportion, infiltration and activation of NK cells, whereas it did not affect CD4+ and CD8+ T cells. NK cell depletion reversed gMoxi‐mediated tumour regression. LLC tumour RNA‐Seq indicated that these effects might be related to the inhibition of adrenergic signalling. Surely, β‐blocker propranolol clearly inhibited LLC tumour growth and promoted NK cells, and gMoxi no longer increased tumour regression and promoted NK cells after propranolol treatment. Epinephrine could inhibit NK cell activity, and gMoxi significantly inhibited tumour growth and promoted NK cells after epinephrine treatment. These results demonstrated that gMoxi could promote NK cell antitumour immunity by inhibiting adrenergic signalling, suggesting that gMoxi could be used as a promising therapeutic regimen for the treatment of NSCLC, and it had a great potential in NK cell–based cancer immunotherapy.