Abstract B011: Inhibition of G9a reestablishes the MHC class I loss due to EMT in lung cancer cells

Abstract

The epithelial-to-mesenchymal transition (EMT) is an important phenotype for cancer cells to invade and metastasizes. In addition, cancer cells should escape from the immune system during malignant progression. Here, we aimed to demonstrate the potential of G9a inhibition of EMT in cancer cells and most importantly, the reestablishment of MHC class I expression (MHC-I), one of the important factors associated with the loss of antigenicity of cancer cells. The lung epithelial cancer cell line A549 was cultured under controlled conditions in RPMI culture media supplemented with 10% of bovine fetal serum (BFS), 1% of antibiotics (penicillin and streptomycin), 2% of glutamine in incubator at 37oC and air atmosphere containing 5% of CO2. The tumor growth factor beta (TGFb) exposure for 5 days was used to induce EMT. In addition, another group of A549 cells received TGFb plus the UNC0368 an G9a (a histone methyl transferase) inhibitor for 5 days. Then, cells were evaluated for acquiring mesenchymal cell morphology and MHC-I gene expression (relative quantification). After 5 days, A549 cells exposed to TGFb clearly have gone through EMT by changing their morphology to a fibroblast-like phenotype. Also, the MHC-I gene expression decreased significantly (p=0.0036) after EMT. The G9a inhibitor partially impeded the EMT induced changes in morphology of A549 cells and reestablished the MHC-I gene expression to the control level. In conclusion, G9a inhibition seemed a promising therapeutic target to improve the efficacy of immunotherapies depending on neoantigen expression by cancer cells. However, more studies are necessary and are under way in our laboratory. Citation Format: Heidge Fukumasu, Pedro R.L. Pires, Pedro L.P. Xavier. Inhibition of G9a reestablishes the MHC class I loss due to EMT in lung cancer cells [abstract]. In: Proceedings of the Fourth CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; Sept 30-Oct 3, 2018; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2019;7(2 Suppl):Abstract nr B011.