The role of vitamin A metabolites, otherwise known as retinoids, has long been controversial in both health and disease. Described in two publications, the findings help resolve this controversy and advance the first candidate drugs to switch off the biochemical signaling pathway they engage within cells.

One study, published in the current issue of Nature Immunology and led by Ludwig Princeton’s and graduate student Cao Fang, describes how retinoic acid produced by the immune system’s dendritic cells (DCs) alters them to induce a dangerous tolerance of tumors. This tolerance, the researchers show, diminishes the efficacy of otherwise promising immunotherapies known as dendritic cell vaccines.

They also report the design and preclinical assessment of a candidate drug that inhibits retinoic acid production by both cancer cells and DCs. The compound, KyA33, not only boosts the efficacy of DC vaccines in preclinical studies but also holds promise as an independent cancer immunotherapy.