Cyclooxygenase-dependent tumor growth through evasion of immunity.
van der Veen, A
Girotti, Maria Romina
Reis E Sousa, C
AffiliationImmunobiology Laboratory, The Francis Crick Institute, Lincoln's Inn Fields Laboratory, 44 Lincoln's Inn Fields, London WC2A 3LY, UK
MetadataShow full item record
AbstractThe 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 Braf(V600E) 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 Braf(V600E) mouse melanoma cells, as well as in Nras(G12D) melanoma 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.
CitationCyclooxygenase-dependent tumor growth through evasion of immunity. 2015, 162 (6):1257-70 Cell
- Response to Programmed Cell Death-1 Blockade in a Murine Melanoma Syngeneic Model Requires Costimulation, CD4, and CD8 T Cells.
- Authors: Homet Moreno B, Zaretsky JM, Garcia-Diaz A, Tsoi J, Parisi G, Robert L, Meeth K, Ndoye A, Bosenberg M, Weeraratna AT, Graeber TG, Comin-Anduix B, Hu-Lieskovan S, Ribas A
- Issue date: 2016 Oct
- Host immunity contributes to the anti-melanoma activity of BRAF inhibitors.
- Authors: Knight DA, Ngiow SF, Li M, Parmenter T, Mok S, Cass A, Haynes NM, Kinross K, Yagita H, Koya RC, Graeber TG, Ribas A, McArthur GA, Smyth MJ
- Issue date: 2013 Mar
- Improved antitumor activity of immunotherapy with BRAF and MEK inhibitors in BRAF(V600E) melanoma.
- Authors: Hu-Lieskovan S, Mok S, Homet Moreno B, Tsoi J, Robert L, Goedert L, Pinheiro EM, Koya RC, Graeber TG, Comin-Anduix B, Ribas A
- Issue date: 2015 Mar 18
- Response to BRAF inhibition in melanoma is enhanced when combined with immune checkpoint blockade.
- Authors: Cooper ZA, Juneja VR, Sage PT, Frederick DT, Piris A, Mitra D, Lo JA, Hodi FS, Freeman GJ, Bosenberg MW, McMahon M, Flaherty KT, Fisher DE, Sharpe AH, Wargo JA
- Issue date: 2014 Jul
- Programmed death-1 & its ligands: promising targets for cancer immunotherapy.
- Authors: Shrimali RK, Janik JE, Abu-Eid R, Mkrtichyan M, Khleif SN
- Issue date: 2015