Polarization of M2 Macrophages to Promote Tumor Immune Escape via Il-10 in SCLC but Not NSCLC Patients

Background and Aims: Because of significant differences in pathology, etiology, clinical features, and treatment options between small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC), it is necessary to investigate differences in macrophage polarization and function in SCLC vs. NSCLC. Macrophage polarization and function are important factors in the growth and metastasis of lung cancer. Methods: Peripheral blood and bronchoalveolar lavage fluid (BALF) were collected from 32 SCLC patients, 35 NSCLC patients, and 14 control subjects (CS). Levels of various subtypes of macrophages, monocytes, and regulatory T cells (Tregs) were determined by flow cytometry. Levels of IL-10 in serum and BALF were evaluated using cytometric bead array (CBA). Lung cancer was diagnosed based on the results of hematoxylin-eosin (HE) staining and histochemistry. Results: Total macrophages (CD14+) and frequency of M2 macrophages (CD206+CD14+ or IL-10+CD206+CD14+) were significantly increased in SCLC patients, compared to NSCLC patients. These changes were accompanied by increased levels of IL-10 in BALF of SCLC patients, compared to NSCLC patients. Increased frequency of M2 macrophages and elevated IL-10 concentration in BALF were positively correlated with advanced tumor stage in SCLC. In SCLC patients, levels of M2 macrophages were positively correlated with IL-10 levels but negatively correlated with survival time. In the same group of patients, IL-10 levels in BALF and frequency of IL-10+CD206+CD14+ M2 macrophages were positively correlated with frequency of Foxp3+CD25+CD4+ Tregs. Finally, levels of circulating M2 monocytes were significantly increased after chemotherapy in SCLC patients, compared to NSCLC patients. Conclusions: Compared to NSCLC, SCLC is characterized by strong polarization of M2 macrophages, which promotes tumor immune escape via IL-10. Funding: This work was supported by the following sponsors: the National Natural Science Foundation of China (No. 30972610, 81273240, 91742107, 81570002, and 81700027), the National Key Research and Development Program (No. 2017YFC0910000 and 2017YFD0501300), the Jilin Province Science and Technology Agency (No. 20160101037JC, 20170622009JC, 2017C021, 2017J039, SXGJXX2017-8, JJKH20180197KJ, DBXM154-2018, and 2018SCZWSZX-015), the Norman Bethune Program of Jilin University (2012206), and the fund of the State Key Laboratory of Kidney Diseases at PLA General Hospital. Declaration of Interest: The authors declare no potential conflicts of interest. Ethical Approval: This study was approved by the Ethical Committee of the First Hospital of Jilin University.