Ludwig Lausanne’s Ping-Chih Ho and his colleagues reported in Nature Immunology in October a novel mechanism by which the harsh microenvironment of the tumor enervates tumor-infiltrating T lymphocytes (TILs). They also showed that a common nutritional supplement, nicotinamide riboside (NR), could revive the anti-tumor activity of the TILs. Starved of oxygen and essential nutrients in tumors, TILs adjust metabolic processes to compensate, in part by making more mitochondria (the energy generators of the cell). Meanwhile, prolonged and fruitless stimulation by cancer antigens pushes TILs into an exhausted state. Ping-Chih and his team found that exhausted TILs are packed with dysfunctional mitochondria, mainly because the TILs can’t remove damaged ones. This, they showed, is a cause, not a consequence, of exhaustion. NR has been shown by Ludwig Lausanne researchers and others to improve mitochondrial fitness, so Ping-Chih and his colleagues examined whether it might rescue TILs from terminal exhaustion. Their cell culture experiments showed that NR improved the mitochondrial fitness and function of T cells in conditions resembling those of the tumor. More notably, dietary supplementation with NR stimulated the anti-tumor activity of TILs in mouse models of melanoma and colon cancer. When combined with checkpoint blockade immunotherapies, it also significantly inhibited the growth of tumors in the mice.
This article appeared in the April 2021 issue of Ludwig Link. Click here to download a PDF (1.4 MB).