AI Article Synopsis
- Researchers found that melanoma tumors grow in hosts with a normal immune system by producing prostaglandin E2, which suppresses immune responses and promotes inflammation.
- Removing certain enzymes (cyclooxygenases) in mouse melanoma cells makes them more vulnerable to immune attacks and changes inflammation to favor anti-cancer responses.
- The study suggests that drugs blocking these enzymes could enhance existing immune therapies, like anti-PD-1 treatments, potentially improving cancer treatment effectiveness.
Article 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 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.
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Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4597191 | PMC |
| http://dx.doi.org/10.1016/j.cell.2015.08.015 | DOI Listing |
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