期刊
IMMUNOLOGICAL INVESTIGATIONS
卷 52, 期 5, 页码 616-634出版社
TAYLOR & FRANCIS INC
DOI: 10.1080/08820139.2023.2217843
关键词
CHOP; immune suppression; microRNA-211; myeloid-derived suppressor cells; ovarian cancer; treatment
类别
This study identified miR-211 as a crucial factor in modulating the accumulation and activity of MDSCs in ovarian cancer (OC)-bearing mice. Upregulation of miR-211 inhibited MDSC proliferation, suppressed immunosuppressive functions, and increased co-incubated CD4+ and CD8+ cell numbers. Moreover, miR-211 overexpression led to decreased activities of the NF-kappa B, PI3K/Akt, and STAT3 pathways, resulting in the downregulation of matrix metalloproteinases and promotion of tumor cell invasion and metastasis. CHOP overexpression countered the effects of miR-211 elevation on these phenotypic changes. Upregulation of miR-211 also impaired MDSC activity and suppressed OC tumor growth in vivo.
BackgroundMyeloid-derived suppressor cells (MDSCs) are capable of effectively repressing immune responses against tumors and orchestrating the tumor microenvironment, which can promote tumor angiogenesis and metastasis. The pathway networks used to modulate tumor-expanded MDSC accumulation and function remain unclear. This study identified microRNA-211 (miR-211), whose expression was significantly decreased by factors derived from tumors.MethodsmiR-211 was assumed to be critical in modulating the accumulation and activity of MDSCs isolated from ovarian cancer (OC)-bearing mice by targeting C/EBP homologous protein (CHOP).ResultsThe upregulation of miR-211 repressed MDSC proliferation, inhibited MDSC immunosuppressive functions, and increased the number of co-incubated CD4+ and CD8+ cells. Furthermore, overexpression of miR-211 led to decreased activities of the NF-kappa B, PI3K/Akt, and STAT3 pathways and the subsequent downregulation of matrix metalloproteinases to promote tumor cell invasion and metastasis. CHOP overexpression counteracted the effects of miR-211 elevation on these phenotypic changes. Upregulation of miR-211 also dramatically impaired the activity of MDSCs and suppressed OC tumor growth in vivo.ConclusionThese results indicated that the miR-211-CHOP axis in MDSCs plays an essential role in the metastasis and proliferation of tumor-expanded MDSCs and might represent a promising cancer treatment target.
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