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dc.contributor.author
Gómez Valenzuela, Fernán
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Wichmann, Ignacio
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Suárez, Felipe José
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Kato, Sumie
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Ossandón, Enrique
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Hermoso, Marcela
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Fernandez, Elmer Andres
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dc.contributor.author
Cuello, Mauricio A.
dc.date.available
2024-04-04T11:51:05Z
dc.date.issued
2023-12
dc.identifier.citation
Gómez Valenzuela, Fernán; Wichmann, Ignacio; Suárez, Felipe José; Kato, Sumie; Ossandón, Enrique; et al.; Cyclooxygenase-2 Blockade Is Crucial to Restore Natural Killer Cell Activity before Anti-CTLA-4 Therapy against High-Grade Serous Ovarian Cancer; Multidisciplinary Digital Publishing Institute; Cancers; 16; 1; 12-2023; 1-19
dc.identifier.issn
2072-6694
dc.identifier.uri
http://hdl.handle.net/11336/231869
dc.description.abstract
Chronic 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.format
application/pdf
dc.language.iso
eng
dc.publisher
Multidisciplinary Digital Publishing Institute
dc.rights
info:eu-repo/semantics/openAccess
dc.rights.uri
https://creativecommons.org/licenses/by/2.5/ar/
dc.subject
NK cells
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immunotherapy
dc.subject
ovarian cancer
dc.subject.classification
Bioquímica y Biología Molecular
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Ciencias Biológicas
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CIENCIAS NATURALES Y EXACTAS
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dc.title
Cyclooxygenase-2 Blockade Is Crucial to Restore Natural Killer Cell Activity before Anti-CTLA-4 Therapy against High-Grade Serous Ovarian Cancer
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2024-03-26T15:23:50Z
dc.journal.volume
16
dc.journal.number
1
dc.journal.pagination
1-19
dc.journal.pais
Estados Unidos
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dc.description.fil
Fil: Gómez Valenzuela, Fernán. Pontificia Universidad Católica de Chile; Chile
dc.description.fil
Fil: Wichmann, Ignacio. Pontificia Universidad Católica de Chile; Chile
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Fil: Suárez, Felipe José. Pontificia Universidad Católica de Chile; Chile
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Fil: Kato, Sumie. Pontificia Universidad Católica de Chile; Chile
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Fil: Ossandón, Enrique. Pontificia Universidad Católica de Chile; Chile
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Fil: Hermoso, Marcela. Universidad de Chile.; Chile
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Fil: Fernandez, Elmer Andres. Fundación Para El Progreso de la Medicina; Argentina. Universidad Nacional de Córdoba; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba; Argentina
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Fil: Cuello, Mauricio A.. Pontificia Universidad Católica de Chile; Chile
dc.journal.title
Cancers
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.3390/cancers16010080
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