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dc.contributor.authorPelly, Victoria S
dc.contributor.authorMoeini, Agrin
dc.contributor.authorRoelofsen, L. M.
dc.contributor.authorBonavita, Eduardo
dc.contributor.authorBell, Charlotte R
dc.contributor.authorHutton, Colin
dc.contributor.authorBlanco-Gomez, Adrian
dc.contributor.authorBanyard, Antonia
dc.contributor.authorBromley, Christian P
dc.contributor.authorFlanagan, Eimear
dc.contributor.authorChiang, Shih-Chieh
dc.contributor.authorJorgensen, Claus
dc.contributor.authorSchumacher, T. N.
dc.contributor.authorThommen, D
dc.contributor.authorZelenay, Santiago
dc.date.accessioned2021-07-19T10:28:53Z
dc.date.available2021-07-19T10:28:53Z
dc.date.issued2021en
dc.identifier.citationPelly VS, Moeini A, Roelofsen LM, Bonavita E, Bell CR, Hutton C, et al. Anti-inflammatory drugs remodel the tumor immune environment to enhance immune checkpoint blockade efficacy. Cancer Discov. 2021 May 24;candisc.1815.2020.en
dc.identifier.pmid34031121en
dc.identifier.doi10.1158/2159-8290.Cd-20-1815en
dc.identifier.urihttp://hdl.handle.net/10541/624129
dc.description.abstractIdentifying strategies to improve the efficacy of immune checkpoint blockade (ICB) remains a major clinical need. Here, we show that therapeutically targeting the COX-2/PGE2/EP2-4 pathway with widely used non-steroidal and steroidal anti-inflammatory drugs synergized with ICB in mouse cancer models. We exploited a bilateral surgery model to distinguish responders from non-responders shortly following treatment and identified acute IFN-γ-driven transcriptional remodeling in responder mice, which was also associated with patient benefit to ICB. Monotherapy with COX-2 inhibitors or EP2-4 PGE2 receptor antagonists rapidly induced this response program and, in combination with ICB, increased the intratumoral accumulation of effector T cells. Treatment of patient-derived tumor fragments from multiple cancer types revealed a similar shift in the tumor inflammatory environment to favor T cell activation. Our findings establish the COX-2/PGE2/EP2-4 axis as an independent immune checkpoint and a readily translatable strategy to rapidly switch the tumor inflammatory profile from cold to hot.en
dc.language.isoenen
dc.relation.urlhttps://dx.doi.org/10.1158/2159-8290.Cd-20-1815en
dc.titleAnti-inflammatory drugs remodel the tumor immune environment to enhance immune checkpoint blockade efficacyen
dc.typeArticleen
dc.contributor.departmentCancer Inflammation and Immunity, CRUK Manchester Institute.en
dc.identifier.journalCancer Discoveryen
dc.description.noteen]
refterms.dateFOA2021-07-26T11:54:19Z


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