TET family dioxygenases and the TET activator vitamin C in immune responses and cancer

Abstract

Vitamin C serves as a cofactor for Fe(II) and 2-oxoglutarate–dependent dioxygenases including TET family enzymes, which catalyze the oxidation of 5-methylcytosine into 5-hydroxymethylcytosine and further oxidize methylcytosines. Loss-of-function mutations in epigenetic regulators such as TET genes are prevalent in hematopoietic malignancies. Vitamin C deficiency is frequently observed in cancer patients. In this review, we discuss the role of vitamin C and TET proteins in cancer, with a focus on hematopoietic malignancies, T regulatory cells, and other immune system cells. (Blood. 2020;136(12):1394-1401)