Abstract 1494: Galectin 9 associates with PDL1 expression and promotes gastric cancer cell invasion

Abstract

Abstract Background: The development of immune checkpoint inhibitors (immunotherapy, such as anti-PD1) that induce a sustained T-cell immune response with anti-tumor activity has been a breakthrough in oncology practice. However, in gastric cancer (GC), sustained responses to anti PD-1 therapy are only observed in approximately 20% of patients. The expression of alternative immune checkpoints such as Galectin 9 (Gal-9) and Tim3 has been associated to anti-PD1 resistance in other cancer types. In search of the factors that render gastric tumors resistant to immunotherapy, we hypothesized that Gal-9 expression in gastric cancer cells may enhance metastasis and immunosuppression. Methods: Bioinformatic analysis of gastric cancer data of patients with gastric adenocarcinoma from TCGA Database was performed. In vitro experiments with Gal-9 transfected gastric cancer cell line AGS were performed to elucidate Gal-9 gain of function effect on cell invasion and immune-suppressive proteins. Invasion assay using a matrigel coated transwell was performed within 24 hours of transfection. To determine changes in PDL1, E-Cadherin and N-Cadherin expression, cells were harvested 24h after transfection to analyze protein and mRNA levels through Western Blot and RT-PCR respectively. Results: TCGA database analysis demonstrate that Gal-9 expression is significantly correlated to PDL-1 expression in gastric cancer; furthermore, it was also positively correlated to immune cell markers such as FOXP3. In accordance, in vitro analysis demonstrates that exogenous expression of GAL9 results in an increase in PDL-1 protein and greater invasive potential of the AGS cell line. Conclusion: Taken together our results suggest that further studies should focus on the role played by Gal-9 is the establishment of an immune suppressive microenvironment in gastric tumors. FONDECYT 1180241, 1180173. CONICYT FONDAP 15130011, IMII P09/016F BMS CA209-8F3 Citation Format: Charlotte Hill, Camille Cabrolier, Elisa Cumsille, Maximiliano Arce, Mauricio P. Pinto, Maria Loreto Bravo, Matias Muñoz, Marcelo Garrido, Gareth I. Owen. Galectin 9 associates with PDL1 expression and promotes gastric cancer cell invasion [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1494.