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

Grain-sized moxibustion promotes NK cell antitumour immunity by inhibiting adrenergic signalling in non-small cell lung cancer.
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颗粒大小的艾灸通过抑制非小细胞肺癌的肾上腺素能信号传导促进NK细胞抗肿瘤免疫。

DOI:
10.1111/jcmm.16320
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发表时间:
2021-03
影响因子:
5.3
通讯作者:
Zhu S
Zhu S
中科院分区:
医学2区
文献类型:
--
作者:
Hu D;Shen W;Gong C;Fang C;Yao C;Zhu X;Wang L;Zhao C;Zhu S

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肺癌是全球癌症相关死亡的主要原因,非小细胞肺癌 (NSCLC) 占肺癌诊断的 85%。作为一种古老的疗法,艾灸在临床实践中已被用于治疗癌症相关症状。然而,其对非小细胞肺癌的抗肿瘤作用在很大程度上仍未被探索。在本研究中,建立了Lewis肺癌(LLC)异种移植肿瘤模型,并在足三里(ST36)穴位进行了颗粒灸(gMoxi)。使用流式细胞术和 RNA 测序 (RNA-Seq) 来了解免疫细胞表型、细胞毒性和基因表达。 PK136、普萘洛尔和肾上腺素分别用于自然杀伤 (NK) 细胞耗竭、β-肾上腺素受体阻断和激活。结果表明,gMoxi 显着抑制 LLC 肿瘤生长。此外,gMoxi 显着增加 NK 细胞的比例、浸润和活化,但不影响 CD4+ 和 CD8+ T 细胞。 NK 细胞耗竭逆转了 gMoxi 介导的肿瘤消退。 LLC 肿瘤 RNA-Seq 表明这些效应可能与肾上腺素能信号传导的抑制有关。当然,β-受体阻滞剂普萘洛尔明显抑制 LLC 肿瘤生长并促进 NK 细胞,而 gMoxi 在普萘洛尔治疗后不再促进肿瘤消退并促进 NK 细胞。肾上腺素可以抑制NK细胞活性,gMoxi在肾上腺素治疗后显着抑制肿瘤生长并促进NK细胞生长。这些结果表明,gMoxi可以通过抑制肾上腺素能信号传导来促进NK细胞抗肿瘤免疫,这表明gMoxi可以作为治疗NSCLC的有前途的治疗方案,并且在基于NK细胞的癌症免疫治疗中具有巨大的潜力。
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.
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