Synthetic RORγ agonists regulate multiple pathways to enhance antitumor immunity.

ABSTRACT: RORγt is the key transcription factor controlling the development and function of CD4⁺ Th17 and CD8⁺ Tc17 cells. Across a range of human tumors, about 15% of the CD4⁺ T cell fraction in tumor-infiltrating lymphocytes are RORγ+ cells. To evaluate the role of RORγ in antitumor immunity, we have identified synthetic, small molecule agonists that selectively activate RORγ to a greater extent than the endogenous agonist desmosterol. These RORγ agonists enhance effector function of Type 17 cells by increasing the production of cytokines/chemokines such as IL-17A and GM-CSF, augmenting expression of co-stimulatory receptors like CD137, CD226, and improving survival and cytotoxic activity. RORγ agonists also attenuate immunosuppressive mechanisms by curtailing Treg

SUBMITTER: Hu X 

PROVIDER: S-EPMC5215247 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature