News Releases & Research Results Elucidation of a novel acquired resistance mechanism for immune checkpoint inhibitors via prostaglandin E2 - Application to new immunotherapy -

The results of the research project conducted by the Research Center for Zoonosis Control, Graduate School of Veterinary Medicine, Hokkaido University and the New Industry Creation Hatchery Center/Department of Antibody Drug Development, Graduate School of Medicine, Tohoku University.

• A novel acquired resistance mechanism by which prostaglandin E2 (PGE2), induced after treatment with immune checkpoint inhibitor "anti-PD-L1 antibody," reduces the effects of the antibody treatment was successfully elucidated.
• Specifically, prostaglandin E2 inhibited T cell activation via the EP4 receptor in bovines. Furthermore, the combination of anti-PD-L1 antibody and EP4 inhibitor had enhanced antitumor effects on mouse lymphoma.
• The results of this research project verified the previous research results on immunotherapy in livestock using a mouse model and should apply to immunotherapy in humans, as well as livestock, because various animal species may have the same mechanism.

This project was conducted with the support of the Platform Project for Supporting Drug Discovery and Life Science Research by AMED.

The results of this research project were published in ImmunoHorizons on December 21.

Sajiki Y., et al. Enhanced immunotherapeutic efficacy of anti-PD-L1 antibody in combination with an EP4 antagonist ImmunoHorizons
DOI: 10.4049/immunohorizons.2000089