OX40/OX40L: A New Target for Tumor Immunotherapy and Its Clinical Research Progress

Abstract The OX40 and OX40L signaling axis represents a key costimulatory pathway in the TNF and TNFR superfamilies. In tumor immunotherapy, OX40L binds to OX40 on activated T cells to promote T cell expansion and cytokine production while inhibiting the inhibitory activity of Tregs and amplifying antitumor immune responses. Clinical trials have shown that OX40 agonists inhibit tumor progression and induce long-lasting systemic immune memory. Several OX40 agonist-based antibodies are currently in early phase I/II clinical studies and have shown good safety and tolerability and great therapeutic potential. This article reviews the OX40/OX40L pathway-related molecular structure, signaling mechanism, regulatory role in the tumor microenvironment and targeted therapy strategies. This article also summarizes some clinical trials using OX40 agonists, analyzes the existing problems and limitations of current therapies, proposes solutions to solve them, and proposes future development directions.