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- W4313374639 startingPage "90.6" @default.
- W4313374639 abstract "Abstract The disseminated of Ovarian cancer (OC) cells shape the tumor abdominal immune environment (TAIE) for survival. However, the key genes and mechanisms mediating the reprogramming of TAIE by OC remain largely unexplored. Here, through a genome-wide in vivo knockout screening by CRISPR/Cas9, we identified IL-20-IL20RA as a key checkpoint preventing the abdominal metastasis of OC cells. In OC patients, the level of IL20RA dramatically decreases in metastatic OC cells when compared with paired OC specimen in the primary sites. Ectopic expression of IL20RA in highly metastatic OC cells greatly suppressed the abdominal metastasis and reduced the formation of ascites. In contrast, silencing IL20RA could increase the metastasis of OC cells. We further examined IL02RA mediated crosstalk between the disseminated cancer cells and the TAIE in both in vivo and in vitro. Silencing IL20RA in OC cells dramatically decreased the M1 macrophages and increased the M2 subtype, while the populations of T and B lymphocytes in ascites were not affected. Further mechanistic studies revealed that the OC cells greatly induced the mesothelial cells in peritoneum to produce IL20RA ligands, i.e., IL-20 and IL-24, which in turn activated the IL20RA downstream signaling in OC cells to trigger the production and maturation of IL-18. IL-18, when secreted into the microenvironment, was able to promote the polarization of macrophages into M1-subtype to kill the cancer cells. Thus, we identified a novel immune checkpoint IL-20/IL20RA that had to be overcome during the metastasis of OC cells to avert an anti-tumor TAIE, which has the potential to be developed as a novel immunotherapy method for OC." @default.
- W4313374639 created "2023-01-06" @default.
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- W4313374639 date "2020-05-01" @default.
- W4313374639 modified "2023-10-16" @default.
- W4313374639 title "Metastatic ovarian cancer shapes the abdominal immune microenvironment by manipulating IL20-IL20RA signaling pathway" @default.
- W4313374639 doi "https://doi.org/10.4049/jimmunol.204.supp.90.6" @default.
- W4313374639 hasPublicationYear "2020" @default.
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