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Cyclooxygenase-Dependent Tumor Growth through Evasion of Immunity

Zelenay, S; van der Veen, AG; Boettcher, JP; Snelgrove, KJ; Rogers, N; Acton, SE; Chakravarty, P; ... Reis e Sousa, C; + view all (2015) Cyclooxygenase-Dependent Tumor Growth through Evasion of Immunity. Cell , 162 (6) pp. 1257-1270. 10.1016/j.cell.2015.08.015. Green open access

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Abstract

The mechanisms by which melanoma and other cancer cells evade anti-tumor immunity remain incompletely understood. Here, we show that the growth of tumors formed by mutant BrafV600E mouse melanoma cells in an immunocompetent host requires their production of prostaglandin E2, which suppresses immunity and fuels tumor-promoting inflammation. Genetic ablation of cyclooxygenases (COX) or prostaglandin E synthases in BrafV600E mouse melanoma cells, as well as in NrasG12Dmelanoma or in breast or colorectal cancer cells, renders them susceptible to immune control and provokes a shift in the tumor inflammatory profile toward classic anti-cancer immune pathways. This mouse COX-dependent inflammatory signature is remarkably conserved in human cutaneous melanoma biopsies, arguing for COX activity as a driver of immune suppression across species. Pre-clinical data demonstrate that inhibition of COX synergizes with anti-PD-1 blockade in inducing eradication of tumors, implying that COX inhibitors could be useful adjuvants for immune-based therapies in cancer patients.

Type: Article
Title: Cyclooxygenase-Dependent Tumor Growth through Evasion of Immunity
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.cell.2015.08.015
Publisher version: http://doi.org/10.1016/j.cell.2015.08.015
Language: English
Additional information: Copyright © 2015 The Authors. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Haematology
URI: http://discovery.ucl.ac.uk/id/eprint/1479620
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