Tumor ammonia levels inhibit T cell growth, impact immunotherapy: Study (Ornithine may address it)

Medical Xpress / University of Michigan / Cell Metabolism ^ | Dec. 23, 2022 | Anna Megdell / Hannah N. Bell et al

[ConservativeMind]

High levels of ammonia in tumors leads to fewer T cells and immunotherapy resistance in mouse models of colorectal cancer, findings revealed. Researchers found that ammonia inhibits the growth and function of T cells, which are vital for anti-tumor immunity.

"We identified the mechanism of how ammonia dysregulates T cell function and showed that reducing ammonia levels using FDA-approved drugs for hyperammonemia can reduce tumor size in several different models including metastatic colorectal cancer," says Hannah Bell, Ph.D. "Use of this drug also synergizes with immunotherapy. If you treat mice with immunotherapy when you also treat them with this ammonia reducing agent, you're able to sensitize the tumors to treatment."

Bell explains that while there are many factors that contribute to immunotherapy resistance, there are few therapeutic interventions that reactivate therapy sensitivity. "Our study shows that this is a relatively safe and FDA-approved method that could work alongside immunotherapy to make treatment more effective for patients. This new method provides a potentially direct avenue to treat tumors and reactivate the immune system."

How does ammonia accumulate in colorectal tumors in the first place? Ammonia levels are regulated by a balance of production and cellular detoxification. Most ammonia is generated by the microbiota, but Bell work suggests that increased production of ammonia is not what results in accumulation. "Our work demonstrates tumors have lost the ability to detoxify ammonia leading to build up," said Shah.

Further, the accumulation of ammonia is likely not isolated to just colorectal tumors. Shah says this discovery may open doors in explaining resistance to other cancer types as well. "Only about 20-30% of all cancer patients are sensitive to immunotherapy. 70% of patients don't derive any benefit from it," Shah said. "Now, we have a mechanism that could explain this resistance in tumors beyond colon cancer."

[ConservativeMind]

Access to the study is behind a paywall, but the graphic with the abstract appears to give the “FDA-approved” solution away. They show ornithine, which is used in our bodies to get rid of ammonia.

Ornithine is a commonly available supplement.

[ConservativeMind]

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[Bayard]

Cancer, always one step ahead.

[T.B. Yoits]

A few years back, a neighbor's dog was riddled with cancer, and had bumps all over under its fur. I swore it smelled like ammonia although my neighbor couldn't smell anything.

Sadly, it didn't survive despite chemotherapy.

[silent majority rising]

I always wondered if the fact that some dogs can smell cancer cells might be from the ammonia levels being different levels than healthy tissue. Any suggestions?

[wgmalabama]

Cancer is a condition that is thought of a disease to be cured. The fact is, I don’t think any two cancers are the same. Even in a specific classification, such as leukemia, it is a unique genetic cellular condition that is broadly grouped based on shared genetic features. Hence why some are cured, some achieve non lasting remission and unfortunately for others is doesn’t even slow. Each individual cancer has a host of genetic failures, omissions, translocation….

The future end of cancer will be to target the patients unique disease.