RORγT agonists as immune modulators in anticancer therapy

Abstract

RORγT is a transcription factor that directs the development of Th17 lymphocytes and other IL-17-expressing cells (e.g., Tc17 and ILC3 cells). These cells are involved in the body's defense against pathogenic bacteria and fungi, but they also participate in maintaining the proinflammatory environment in some autoimmune diseases and play a role in the immune system's response to cancer. Similar to other members of the nuclear receptor superfamily, the activity of RORγT is regulated by low-molecular-weight ligands. Therefore, extensive efforts have been dedicated to identifying inverse agonists that diminish the activity of this receptor and subsequently inhibit the development of autoimmune diseases. Unfortunately, in the pursuit of an ideal inverse agonist, the development of agonists has been overlooked. It is important to remember that these types of compounds, by stimulating lymphocytes expressing RORγT (Th17 and Tc17), can enhance the immune system's response to tumors. In this review, we present recent advancements in the biology of RORγT agonists and their potential application in anticancer therapy.

Keywords: Adoptive therapy; Agonists; Immune system stimulation; RORγT; Tc17; Th17.