The cores of tumors are often acidic and starved of oxygen and vital nutrients. This forces resident cells to adapt their metabolism to survive. Ludwig Lausanne’s Ping-Chih Ho and colleagues reported in a February paper in Nature Immunology a novel mechanism by which regulatory T cells (Tregs), which suppress immune responses and autoimmunity, adapt their metabolism to deal with the acidity. The mechanism, Ping-Chih and his team found, is exclusively engaged by Tregs that reside in tumors and could be selectively disrupted in a mouse model to boost immunotherapy without inducing autoimmune side effects. They discovered that intratumoral Tregs express high levels of genes involved in lipid uptake and metabolism—particularly CD36, a receptor involved in lipid import. CD36 deficiency induced in intratumoral Tregs a form of cell suicide known as apoptosis, driven by a decline in their mitochondria, the power generators of cells. Likewise, treating mice bearing melanoma tumors with an antibody to CD36 resulted in the decimation of intratumoral Tregs (though not other Tregs) and boosted the effects of anti-PD-1 immunotherapy, which stimulates a T cell attack on cancer cells. Ping-Chih’s lab is now working to translate these findings into a potential cancer therapy.
This article appeared in the August 2020 issue of Ludwig Link. Click here to download a PDF (1.7 MB).