Triple-negative breast cancer: Tumor metabolite aids cancer's escape from immune system
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.
Researchers from the GIGA Institute have discovered that methylglyoxal, a byproduct of tumor metabolism, plays a crucial role in the immune evasion of triple-negative breast cancer. This study, published in the Journal for ImmunoTherapy of Cancer, indicates that elevated levels of methylglyoxal stress lead to an increase in immunosuppressive granulocyte-derived myeloid-derived suppressor cells (g-MDSCs), which in turn promotes tumor progression and resistance to immunotherapy.
The research was conducted in collaboration with various universities and research institutes in Belgium and Luxembourg. Lead researcher Victoria Mohring and her team found that methylglyoxal stress is linked to the accumulation of g-MDSCs, which suppress antitumor responses and help tumors evade immune surveillance. They also discovered that a specific gene signature associated with methylglyoxal stress can predict whether melanoma patients will respond to PD-1-targeting immunotherapy.
The team further demonstrated that neutralizing methylglyoxal using carnosine, a molecule that can trap it, reduces the accumulation of g-MDSCs and the lung metastasis in preclinical models of triple-negative breast cancer resistant to immunotherapy. This finding suggests that targeting tumor metabolism and immune escape mechanisms simultaneously could be a promising strategy for combating cancers that resist immunotherapy.
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