Cyclooxygenase-2 Blockade Is Crucial to Restore Natural Killer Cell Activity before Anti-CTLA-4 Therapy against High-Grade Serous Ovarian Cancer

Simple item page
dc.catalogadorgrr
dc.contributor.authorGómez-Valenzuela, Fernán
dc.contributor.authorWichmann Pérez, Ignacio Alberto
dc.contributor.authorSuárez, Felipe
dc.contributor.authorKato Cardemil, Sumie Rode
dc.contributor.authorOssandón, Enrique
dc.contributor.authorHermoso, Marcela
dc.contributor.authorFernández, Elmer A.
dc.contributor.authorCuello, Mauricio A.
dc.date.accessioned2023-12-26T18:41:41Z
dc.date.available2023-12-26T18:41:41Z
dc.date.issued2023
dc.description.abstractChronic inflammation influences the tumor immune microenvironment (TIME) in high-grade serous ovarian cancer (HGSOC). Specifically, cyclooxygenase-2 (COX-2) overexpression promotes cytotoxic T-lymphocyte-associated protein-4 (CTLA-4) expression. Notably, elevated COX-2 levels in the TIME have been associated with reduced response to anti-CTLA-4 immunotherapy. However, the precise impact of COX-2, encoded by PTGS2, on the immune profile remains unknown. To address this, we performed an integrated bioinformatics analysis using data from the HGSOC cohorts (TCGA-OV, n = 368; Australian cohort AOCS, n = 80; GSE26193, n = 62; and GSE30161, n = 45). Employing Gene Set Variation Analysis (GSVA), MIXTURE and Ecotyper cell deconvolution algorithms, we concluded that COX-2 was linked to immune cell ecosystems associated with shorter survival, cell dysfunction and lower NK cell effector cytotoxicity capacity. Next, we validated these results by characterizing circulating NK cells from HGSOC patients through flow cytometry and cytotoxic assays while undergoing COX-2 and CTLA-4 blockade. The blockade of COX-2 improved the cytotoxic capacity of NK cells against HGSOC cell lines. Our findings underscore the relevance of COX-2 in shaping the TIME and suggest its potential as a prognostic indicator and therapeutic target. Increased COX-2 expression may hamper the effectivity of immunotherapies that require NK cell effector function. These results provide a foundation for experimental validation and clinical trials investigating combined therapies targeting COX-2 and CTLA-4 in HGSOC.
dc.fechaingreso.objetodigital2023-12-26
dc.format.extent19 páginas
dc.fuente.origenORCID
dc.identifier.doi10.3390/cancers16010080
dc.identifier.eissn2072-6694
dc.identifier.urihttps://doi.org/10.3390/cancers16010080
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/75566
dc.information.autorucEscuela de Medicina; Wichmann Pérez, Ignacio Alberto; 0000-0002-1115-2937; 149908
dc.information.autorucEscuela de Medicina; Kato Cardemil, Sumie Rode; S/I; 82640
dc.issue.numero1
dc.languageen
dc.language.isoen
dc.nota.accesoContenido completo
dc.revistaCancers
dc.rightsacceso abierto
dc.rights.holderAtribución 4.0 Internacional (CC BY 4.0)
dc.solicitanteHigh-grade serious ovarian cancer
dc.solicitanteCyclooxygenase-2
dc.subjectTumor immune microenvironment
dc.subjectCytotoxic T-lymphocyte-associated protein-4
dc.subjectImmunotherapy
dc.subjectNK cells
dc.subjectHigh-grade serious ovarian cancer
dc.subjectCyclooxygenase-2
dc.subject.ddc610
dc.subject.deweyMedicina y saludes_ES
dc.titleCyclooxygenase-2 Blockade Is Crucial to Restore Natural Killer Cell Activity before Anti-CTLA-4 Therapy against High-Grade Serous Ovarian Cancer
dc.typeartículo
dc.volumen16
sipa.codpersvinculados149908
sipa.codpersvinculados82640
sipa.trazabilidadORCID;2023-12-25
Files
Original bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
cancers-16-00080-v2.pdf
Size:
7.21 MB
Format:
Adobe Portable Document Format
Description:
Download
Collections
Artículos de revistas