Ammonia, which accumulates intensively in the tumor microenvironment, supports cancer progression by weakening the immune system’s response – according to groundbreaking research led by Dr. Magdalena Winiarska from the Mossakowski Medical Research Institute, Polish Academy of Sciences. These findings may help increase the effectiveness of immunotherapy.
Ammonia (NH₃) is a chemical compound naturally produced in cells during amino acid metabolism. In excess, it is toxic, which is why the body quickly eliminates it – primarily via the liver and, to a lesser extent, the kidneys, where it is converted into urea and excreted.
Recent discoveries made by Polish scientists have revealed that ammonia tends to accumulate in solid tumors. Rapidly dividing cancer cells not only produce large amounts of ammonia but also have limited capacity to remove it due to factors like poor blood supply. More and more evidence suggests that ammonia is not just a byproduct but may actively support tumor growth. Some cancer cells even repurpose ammonia to build cellular biomass.
The new study, published in the journal Cancer Research, sheds light on another harmful aspect of ammonia: its suppression of the immune system. The research team demonstrated that ammonia impairs the function of natural killer (NK) cells and T lymphocytes – both crucial components in the body’s defense against cancer.
This immunosuppressive effect of ammonia not only hinders the natural immune response but also reduces the efficacy of immunotherapy – including advanced therapies involving monoclonal antibodies, CAR-T, and CAR-NK cells. These cutting-edge approaches involve genetically modifying a patient’s immune cells to recognize and eliminate cancer cells.
The new insights suggest promising directions for future research. One potential strategy could involve equipping immune cells with enzymes capable of neutralizing ammonia, thereby restoring their full cytotoxic potential. Another possibility is to develop methods that help perforin maintain its activity even in ammonia-rich environments.
“Ammonia is just one piece of the puzzle in understanding how tumors evade the immune system,” said Dr. Winiarska. “But thanks to basic research, we are gradually unveiling the complex mechanisms behind disease – and with that knowledge, we can create better treatments. Without basic science, there are no new therapies.”
This research was conducted with the support of a grant from the European Research Council (ERC).
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