Tumors recycle glucocorticoids to drive Treg-mediated immunosuppression

Suppression of antitumor immunity is a prominent feature of the tumor microenvironment. In this issue of the JCI, Taves, Otsuka, and authors show that glucocorticoids (GCs), which are potent immunosuppressive hormones mainly produced by the adrenals, can be reconverted from their inactive form to active metabolites via the 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) enzyme expressed by murine tumor cell lines. In the tumor microenvironment, GCs acted on CD4+ regulatory T cells to enhance their immunosuppressive function and promote tumor growth. The findings suggest that targeting GC recycling as a strategy for modulating tumor immunosuppression has the potential to improve therapeutic efficacy of immune checkpoint blockade. © 2023, Swatler et al.