Triple-negative breast cancer: Tumor metabolite aids cancer's escape from immune system
· Medical Xpressedited by Gaby Clark, reviewed by Andrew Zinin
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Cancer cell metabolism may play a key role in tumors' ability to evade the immune system. In a study published in the Journal for ImmunoTherapy of Cancer, researchers from GIGA demonstrate that methylglyoxal, a byproduct of tumor metabolism, contributes to the creation of an environment that favors the progression of triple-negative breast cancer and resistance to immunotherapy.
Led by Ph.D. candidate Victoria Mohring, with support from Télévie-FNRS, under the supervision of Professor Akeila Bellahcène, FNRS research director, the study was carried out within the GIGA Metastasis Research Laboratory in collaboration with several teams from the University of Liège, Université libre de Bruxelles (ULB) and the Luxembourg Institute of Health (LIH).
When metabolism fuels cancer progression
To grow rapidly, cancer cells alter their metabolism and consume large quantities of glucose. This activity generates methylglyoxal (MG), a highly reactive molecule already identified as a key factor in tumor progression and metastatic spread in triple-negative breast cancer.
Previous work carried out by teams at the GIGA Institute (University of Liège) had shown that an imbalance between the production of methylglyoxal and its detoxification by the glyoxalase system—known as "methylglyoxal stress"—promotes the formation of metastases. This time, the researchers sought to understand how this phenomenon influences the tumor's immune environment.
An immune environment hijacked for the benefit of the tumor
Using preclinical breast cancer models and patient data, Mohring and her colleagues identified a close link between methylglyoxal stress and the accumulation of granulocyte-derived myeloid-derived suppressor cells (g-MDSCs). These immune cells are known to suppress antitumor responses and help tumors evade immune surveillance.
The findings suggest that methylglyoxal stress stimulates the expansion of these immunosuppressive cells, notably through the activation of specific inflammatory pathways and the upregulation of factors that promote their recruitment. In data from patients with triple-negative breast cancer, a gene signature associated with methylglyoxal stress also correlates with markers of g-MDSC infiltration.
A potential indicator of response to immunotherapy
The researchers also observed that this molecular signature could be used to distinguish between melanoma patients who do and do not respond to PD-1-targeting immunotherapy. This observation suggests that the level of methylglyoxal stress could be associated with the efficacy of certain immunotherapy treatments.
These results reinforce the idea that tumor metabolism is not limited to supplying energy to cancer cells but plays an active role in reshaping their immune environment.
Targeting methylglyoxal to limit metastases
The team then explored a therapeutic approach aimed at neutralizing methylglyoxal using carnosine, a molecule capable of trapping it. In a model of triple-negative breast cancer resistant to immunotherapy, this strategy, combined with anti-PD-1 treatment, reduced the accumulation of g-MDSCs as well as the pulmonary metastatic burden.
"These results highlight a direct link between the metabolic vulnerability of tumor cells and their ability to remodel their immune microenvironment," Bellahcène says. "They also suggest that combined targeting of tumor metabolism and immune escape mechanisms could constitute a new strategy for combating cancers resistant to immunotherapy."
Toward new therapeutic strategies
Beyond triple-negative breast cancer, this study highlights the still largely underestimated role of tumor metabolism in the response to treatment. It paves the way for the development of new approaches combining immunotherapy and metabolic targeting to restore the immune system's defenses against cancer cells and limit the formation of metastases.
This research also offers new prospects for identifying biomarkers capable of predicting response to immunotherapy and, ultimately, better personalizing patient treatments.
Publication details
Victoria Mohring et al, Turning off methylglyoxal stress: an alternative approach to inhibit MDSC expansion and metastasis in triple-negative breast cancer, Journal for ImmunoTherapy of Cancer (2026). DOI: 10.1136/jitc-2026-014841
Journal information: Journal for ImmunoTherapy of Cancer
Key medical concepts
Triple Negative Breast Neoplasms
Clinical categories
OncologyAllergy and immunology Provided by University de Liege Who's behind this story?
Gaby Clark
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