Dr. Weeks’ Comment: The term “Guardian of the Genome” is apt. P53 (which stimulates P21 to repair genetic damage) is the prime “tumor suppressor” genetic tool. How is your P53/P21 functioning?
Promising Way to Boost Body’s Immune Surveillance Via P53 in Fight Against Cancer
Sep. 19, 2013 — Researchers at A*STAR’s Singapore Immunology Network (SIgN) have discovered a new mechanism involving p53, the famous tumour suppressor, to fight against aggressive cancers. This strategy works by sabotaging the ability of the cancer cells to hide from the immune system. Published in the Nature Communications journal, this research opens a new avenue to improve targeted cancer therapy by harnessing the body’s own immune system to control and eliminate cancer cells.
In this study, the SIgN team discovered for the first time that the integrity of p53 affects the production of a special cell surface protein called Major Histocompatibility Complex (MHC) class I. MHC class I molecules on the cancer cell surface serve as targets for the immune system. Therefore, having less MHC I molecules may allow cancer cells to hide better and escape detection by the immune system.
Using two cancer cell lines differing only in the integrity of p53 gene, the scientists observed that cancer cells with defective p53 had much less MHC class I on the cell surface. Specifically, they discovered that p53 moderates the expression of MHC I by controlling the amount of another protein called ERAP1 in the cells. Interestingly, a number of disease conditions including tumour malignancy, multiple sclerosis and autoimmune disease were recently reported to be associated with ERAP1.
The team leader, Associate Professor Ren Ee Chee from SIgN said, “We were surprised to discover that p53 regulates MHC class I production by acting through ERAP1. This may explain how cancer cells escape detection by our body’s immune system. More importantly, it opens up exciting avenues of research to explore how restoration of p53 with drugs such as those that target ERAP1 can help to harness the immune system to recognise and destroy cancer cells.”
Acting Executive Director of SIgN, Associate Professor Laurent Rénia said, “The team has uncovered a new door to manipulate one of the most studied yet enigmatic cancer-associated genes of our times. I am confident that this work will pave the way for more targeted, efficient and cost-effective treatment for the millions of cancer patients globally.”
- Bei Wang, Dandan Niu, Liyun Lai, Ee Chee Ren. p53 increases MHC class I expression by upregulating the endoplasmic reticulum aminopeptidase ERAP1. Nature Communications, 2013; 4 DOI: 10.1038/ncomms3359