AUTHOR=Wang Lixin , Wu Wenbin , Zhu Xiaowen , Ng Wanyi , Gong Chenyuan , Yao Chao , Ni Zhongya , Yan Xuewei , Fang Cheng , Zhu Shiguo 

TITLE=The Ancient Chinese Decoction Yu-Ping-Feng Suppresses Orthotopic Lewis Lung Cancer Tumor Growth Through Increasing M1 Macrophage Polarization and CD4+ T Cell Cytotoxicity

JOURNAL=Frontiers in Pharmacology

VOLUME=10

YEAR=2019

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2019.01333

DOI=10.3389/fphar.2019.01333

ISSN=1663-9812

ABSTRACT=<p><bold>Background:</bold> The tumor microenvironment (TME) has a deep influence on cancer progression and has become into a new target for cancer treatment. In our previous study, we found that Yu-Ping-Feng (YPF), an ancient Chinese herbal decoction, significantly inhibited the Lewis lung cancer (LLC) tumor growth in a subcutaneous xenograft tumor model, and prolonged the survival of tumor-bearing mice. But the regulation of Yu-Ping-Feng on tumor microenvironment is unknown.</p><p><bold>Methods:</bold> To access the effect of Yu-Ping-Feng on non-small cell lung cancer, an orthotopic luciferase stably expressed Lewis lung cancer tumor model was established on C57BL/6 mice, and then the survival and the tumor growth were evaluated. To address the tumor microenvironment immune regulation, the percentages of CD4<sup>+</sup> T cells, CD8<sup>+</sup> T cells, natural killer cells (NK), regulatory T cells (Treg), macrophages, and myeloid-derived suppressor cells (MDSC) in spleens and tumor tissues, the macrophage polarization and CD4<sup>+</sup> T cell cytotocixity were analyzed by flow cytometry, biophotonic cell killing activity assay, real-time PCR and western-blot.</p><p><bold>Results:</bold> Yu-Ping-Feng significantly prolonged orthotopic lung tumor-bearing mouse survival, and increased the percentages of CD4<sup>+</sup> T cell and M1 macrophages and the cytotoxicity of CD4<sup>+</sup> T cells. Yu-Ping-Feng significantly enhanced macrophage-mediated lysis of LLC in a concentration-dependent manner, and had no effect on CD4<sup>+</sup> T cell-mediated lysis of LLC, but significantly increased CD4<sup>+</sup> T cell-mediated lysis after co-incubated with macrophages. In addition, Yu-Ping-Feng induced M1 macrophage polarization through promoting the phosphorylation of STAT1.</p><p><bold>Conclusion:</bold> Yu-Ping-Feng induced M1 macrophages polarization, and then activated CD4<sup>+</sup> T lymphocytes, resulting in killing of LLC cells. Yu-Ping-Feng was a potent regulator of M1 macrophage polarization and might have a promising application in tumor immunotherapy.</p>