Galectin 9 promotes invasion and angiogenesis in vitro and associates with an immune-suppressive microenvironment in gastric cancer patients

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dc.coverageDOI: 10.1158/1538-7445.am2021-2792
dc.creatorHill, Charlotte Nicole
dc.creatorArata, Maximiliano Arce
dc.creatorCabrolier, Camille
dc.creatorLuque, Noymar
dc.creatorGonzalez, Pamela
dc.creatorMaita, Gabriela
dc.creatorVega-Letter, Ana Maria
dc.creatorCrawford, Patricia Luz
dc.creatorGarrido, Marcelo
dc.creatorOwen, Gareth I.
dc.date2021
dc.date.accessioned2026-01-05T21:08:49Z
dc.date.available2026-01-05T21:08:49Z
dc.descriptionThe development of immune checkpoint inhibitors is revolutionizing gastric cancer (GC) therapy. However, the presence of an immune-suppressive tumor microenvironment and redundancy between inhibitory immune checkpoints may be responsible for why a high percentage of patients without clinical benefit. An emerging checkpoint target is Tim-3, a membrane protein that enhances immunosuppression upon binding to its ligand Galectin-9 (Gal-9). Gal-9 is overexpressed in gastrointestinal cancers and expressed in both cancer and stromal cells such as the tumor endothelium. However the role of the Gal-9/Tim-3 pathway in the GC tumor microenvironment is still undeciphered, we hypothesize that this pathway mediates immune escape though enhancement of a immunosuppressive microenvironment. We performed a bioinformatic analysis of stomach adenocarcinoma (STAD) from the TCGA database (TIMER©, Cibersort and Xcell were used). To evaluate if Gal-9 had an impact on cancer cell phenotype we transfected Gal-9 into the gastric cancer cell line AGS and the gastric epithelium cell line GES-1. To assess the potential role in CG tumor microenvironment, Gal-9 was transfected or recombinant Gal-9 (rGal-9) was administrated to Human Umbilical Vein Endothelial Cells (HUVECs). Gal-9 biological effects were assessed by migration, invasion and Matrigel tube formation assay. Western blotting assessed Tim-3 expression and PDL-1 expression. Furthermore, we used lactose to block Gal-9 binding to Tim-3 to determine if the biological effects required receptor engagement. Results from TCGA analysis demonstrated that both Gal-9 and Tim-3 are upregulated in gastric tumors. Tim-3 mRNA is significantly increased in invasive adenocarcinomas. A positive correlation was observed between Gal-9, PDL-1 and Tim-3, which was consistent with in vitro experiments, where increased expression of Gal-9 resulted in increased PDL-1 and Tim-3. In addition, Gal-9 increased cancer cell invasion and promoted HUVEC migration and tubular like structure formation in vitro. Further bioinformatic analysis revealed strong positive correlation with CD8+ T cell, Treg and macrophage/monocyte gene signatures. Tim-3 and Gal-9 were more strongly associated with these gene signatures than PD1 and PDL-1. Interestingly, Gal-9 was associated with T cell dysfunction and Treg markers, suggesting that in GC Gal-9 could promote T cell dysfunction and Treg expansion. Our results suggest an association between the Gal-9/Tim-3 pathway with a more aggressive and increased immune suppressive microenvironment and GC.Funding: Fondecyt 118024, CONICYT-FONDAP 15130011, IMIIP09/16F, FONDECYT 1180173Citation Format: Charlotte Nicole Hill, Maximiliano Arce Arata, Camille Cabrolier, Noymar Luque, Pamela Gonzalez, Gabriela Maita, Ana Maria Vega-Letter, Patricia Luz Crawford, Marcelo Garrido, Gareth I. Owen. Galectin 9 promotes invasion and angiogenesis in vitro and associates with an immune-suppressive microenvironment in gastric cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2792.spa
dc.identifierhttps://investigadores.uandes.cl/en/publications/7471a5aa-80b0-4bdf-afa8-0456a99ede7d
dc.identifier.urihttps://repositorio.uandes.cl/handle/uandes/63561
dc.languagespa
dc.rightsinfo:eu-repo/semantics/restrictedAccess
dc.sourcevol.81 (2021) nr.13_Supplement p.2792-2792
dc.subjectODS 3: Salud y bienestar
dc.titleGalectin 9 promotes invasion and angiogenesis in vitro and associates with an immune-suppressive microenvironment in gastric cancer patientsspa
dc.typeMeeting Abstracteng
dc.typeResumen de la jornadaspa
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