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- W4313405845 abstract "Abstract Inactivation of antigen processing and presentation (APP) pathways is one of the major mechanisms for immune evasion in many cancer types including high-grade endometrial cancer (HGEC). Impairments in APP pathways may contribute to the low immunotherapy response rate among the patients. However, lack of pre-clinical models for HGEC poses a significant challenge in studying critical therapeutic aspects of the cancer such as cancer-immune cell interactions. To our knowledge, we have established the largest endometrial biobank comprising primary tissues, patient-derived organoids (PDO), and their matching immune cells from all existing endometrial cancer types, enabling us to establish the interaction between cancer and immune cells in vitro. Using a subset of our biobank, we performed RNA-seq on 68 PDOs and found that genes involved in APP pathways are downregulated in HGEC organoids compared to their matching normal pairs. We found that MHC-I and -II could be upregulated by IFNg and Tazemetostat, an EZH2 inhibitor. We further assessed the effects of enhanced MHC-I and -II expression mediated by the two molecules on cancer-immune cell interactions by setting up syngeneic organoid-immune cell co-cultures. We found that HGEC organoids that were pre-treated with IFNg or Tazemetostat displayed a greater immune cell co-localization and immune cell-mediated apoptosis during the co-culture period. Our proof-of-principle experiments demonstrate the utility of our co-culture system in studying the cancer-immune cell interactions in vitro. Our system could be used to test the efficacy of current therapeutics or to screen potential drugs which enhance immune responses against HGEC, which lacks effective treatment options. This research was supported by grants from The Mark Foundation for Cancer Research (20-028-EDV630), NCI CancerCenter Support Grant (5P30CA045508),and CSHL-northwell transitional research fund." @default.
- W4313405845 created "2023-01-06" @default.
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- W4313405845 date "2022-05-01" @default.
- W4313405845 modified "2023-09-23" @default.
- W4313405845 title "Organoid models for high-grade endometrial cancer to dissect tumor immune microenvironments" @default.
- W4313405845 doi "https://doi.org/10.4049/jimmunol.208.supp.177.04" @default.
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