scholarly journals Plasmodium infection inhibits the expansion and activation of MDSCs and Tregs in the tumor microenvironment in a murine Lewis lung cancer model

2019 ◽  
Vol 17 (1) ◽  
Author(s):  
Dickson Adah ◽  
Yijun Yang ◽  
Quan Liu ◽  
Kranthi Gadidasu ◽  
Zhu Tao ◽  
...  
2020 ◽  
Vol 2020 ◽  
pp. 1-13
Author(s):  
Zhuo Chen ◽  
Xiang Qian ◽  
Shasha Chen ◽  
Xiaoxuan Fu ◽  
Guanjun Ma ◽  
...  

Recently, intestinal flora plays a vital role in the occurrence and development of tumors and there is link between cancer immunotherapy and Akkermansia muciniphila (Akk). However, the therapeutic efficacy of Akk in lung cancer remained unclear. Hence, our study is aimed at investigating the antitumor effects of cisplatin (CDDP) combined with Akk on lung cancer. Using the murine lung cancer model by subcutaneously inoculating Lewis lung cancer model, 50 mice were divided into five groups: normal, model, CDDP, CDDP+Akk, and CDDP+antibiotics. After treatment within 5 weeks, compared with the model group, the administered group improved the changes of tumor pathomorphology. Compared with the CDDP group, CDDP combining with Akk slowed down the growth of tumor volume, downregulated the levels of ki-67, p53, and factor-associated suicide (Fas) ligand proteins and upregulated Fas proteins, increased the levels of interferon-γ, interleukin-6, and tumor necrosis factor-α, and suppressed the expression of CD4+CD25+Foxp3+ Treg in mouse peripheral blood and spleen. In addition, transcriptome analysis indicated that Akk combining with CDDP increased obviously the levels of IFI27l2 and IGFBP7 and was related to those pathways including the cytokine-cytokine receptor interaction, Th17 cell differentiation, FOXO, JAK-STAT, and PI3K-Akt signaling pathways. These results suggested that the therapeutic efficacy of the combined treatment of Akk and CDDP was superior to the only CDDP treatment, which could enhance immune regulation and would be a promising strategy for the treatment of lung cancer.


Oncogenesis ◽  
2017 ◽  
Vol 6 (6) ◽  
pp. e351-e351 ◽  
Author(s):  
Y Yang ◽  
Q Liu ◽  
J Lu ◽  
D Adah ◽  
S Yu ◽  
...  

2011 ◽  
Vol 8 (4) ◽  
pp. 359-367 ◽  
Author(s):  
Yuchan Cai ◽  
Shudao Xiong ◽  
Yijie Zheng ◽  
Feifei Luo ◽  
Pei Jiang ◽  
...  

2009 ◽  
Vol 134 (2) ◽  
pp. 91-97 ◽  
Author(s):  
Jinhui Wu ◽  
Dawei Ding ◽  
Guoyan Ren ◽  
Xiangyang Xu ◽  
Xiaojin Yin ◽  
...  

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Guangping Meng ◽  
Jinying Wei ◽  
Yanjun Wang ◽  
Danhua Qu ◽  
Jie Zhang

Abstract Background Myeloid-derived suppressor cells (MDSCs) are known suppressors of antitumor immunity and contribute to immunosuppressive microenvironment during tumor development including lung cancer. Accumulating evidence shows microRNAs (miRNAs) affect tumor-expanded MDSC accumulation and function in tumor microenvironment and favor solid tumor growth. Herein, we aim to characterize the role of miR-21 in regulating the accumulation and activity of MDSCs in lung cancer. Methods The proportions of MDSCs, T helper cells (Th), and cytotoxic T lymphocytes (CTL) were evaluated by flow cytometric analyses of peripheral blood and tumor tissues collected from Lewis lung-cancer-bearing mice. T cell proliferation assay was performed in CD4+ or CD8+ T cells cocultured with MDSCs. MDSC apoptosis was examined by flow cytometric analysis. The levels of IL-10, TGF-β, and GM-CSF in mouse serum were determined by ELISA. miR-21 targeting RUNX1 and RUNX1 interaction with YAP were evaluated by RIP, dual-luciferase reporter gene, and ChIP assays. Results MiR-21 inhibition by its antagomir reduced the proportion of MDSCs, increased the proportion of Th and CTL in peripheral blood and tumor tissues of Lewis lung-cancer-bearing mice, protected Th and CTL from the suppression of MDSCs, increased apoptosis of MDSCs, but reduced IL-10, TGF-β and GM-CSF levels in mouse serum. RUNX1 could transcriptionally inhibit the YAP expression, whereas miR-21 targeting RUNX1 led to elevated YAP expression levels. Mechanistic investigation showed that miR-21 maintained MDSC accumulation in tumor microenvironment and promoted immunosuppressive ability of MDSCs in Lewis lung-cancer-bearing mice by down-regulating RUNX1and up-regulating YAP. Conclusions Taken together, the study provides evidence that targeting miR-21 in MDSCs may be developed as an immunotherapeutic approach to combat lung cancer development.


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