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A team of Chinese scientists has uncovered a key mechanism behind how breast cancer cells weaponise the amino acid arginine to evade the immune system and multiply.
Their findings could open up a new avenue for precision therapy for what is the most commonly diagnosed cancer among women – through starving the tumours of this essential building block for protein.
The precise metabolic communication through which arginine exerts its effects within the tumour micro-environment – or the complex cellular ecosystem influencing tumour behaviour – has long eluded scientists.
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Researchers from the Chinese Academy of Sciences (CAS) Hangzhou Institute of Medicine and Sun Yat-sen University may now have an answer.
“We reveal that the metabolic interplay between cancer cells and macrophages plays a dominant role in arginine-driven breast cancer progression,” the researchers wrote in a paper published in the peer-reviewed journal Cancer Cell on April 3.
Macrophages are a type of white blood cell that help to clear out dead cells and stimulate other cells involved in immune function.
The team – along with hospital-affiliated researchers – used cell cultures and mice to investigate the role and mechanism behind the progression of breast cancer, which kills hundreds of thousands each year.
Globally, 2.3 million women were diagnosed with breast cancer in 2022, and 670,000 died from it, according to the World Health Organization.
Arginine is a semi-essential or conditionally essential amino acid that can be produced within the body, but some conditions can render them essential, when they must be procured through the diet.
Arginine supports protein growth and healthy immune function and is found in most protein-rich foods, apart from being sometimes consumed as a supplement, mostly to help treat circulatory issues.
Elevated levels of arginine have been observed in advanced breast cancer patients, but there has been no evidence that this was due to the consumption of an arginine-rich diet.
That suggests that the source could be the tumour cells themselves.
The Chinese team found that within the tumour micro-environment, breast cancer cells could act as “arginine factories”, according to a CAS note.
The breast cancer cells saturate the tumour micro-environment with arginine and exploit it to reprogramme a type of immune cell called tumour-associated macrophages. Once these immune cells are reprogrammed, they suppress the main cancer-fighting immune cells in the body – called cytotoxic T lymphocytes – allowing the cancer to progress.
“This study identifies cancer cell-macrophage interaction as the key driver of arginine-mediated tumour progression, highlighting a distinct intercellular mechanism within the breast cancer [tumour micro-environment] that fosters tumour development,” the researchers said in their paper.
They also found that disrupting arginine metabolism could help restore the activity of the T cells and slow tumour growth.
“These findings highlight the potential of targeting arginine metabolic crosstalk between cancer cells and macrophages to counteract tumour-driven immunosuppression,” the team said.
“Further clinical research is required to translate these findings into precision medicine strategies for breast cancer treatment.”
While the researchers focused on arginine-driven breast cancer progression, they suggested that future studies “explore metabolic communication beyond arginine in diverse cancer types to pinpoint the key cell-cell interactions driving immune regulation” – so as to aid the development of more targeted therapeutic strategies.
More from South China Morning Post:
- Chinese scientists turn tumours into ‘pork’ in radical cancer treatment
- China’s molecular ‘elevator’ boosts immunity 150-fold against cancer, viruses: scientists
- US decouples from China in war on cancer, denying access to research databanks
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