The latest paper by Zhu Di’s team at Fudan University: RORγt agonists enhance anti-PD-1 therapy by promoting monocyte-derived dendritic cells through CXCL10 in cancer

On April 23, 2022, Researcher Zhu Di of Fudan University published a paper titled "RORγt agonist enhances anti-PD-1 therapy by promoting monocyte" in the Journal of Experimental & Clinical Cancer Research (IF=11.

The overall response rate to immune checkpoint therapy is limited, in part due to the immunosuppressive tumor microenvironment

RORγt is an isoform of RORγ that is specifically expressed in immune cells, encoded by the Rorc gene, and is the main transcription factor of mouse and human Type 17 T cells, playing an important role in the differentiation and maintenance of Type 17 T cells

Previously, the research team's findings published in 2021 showed that the RORγt agonist JG-1 promotes Th17 cell differentiation and inhibits regulatory T (Treg) cell differentiation

The team further studied and designed a potent and selective small-molecule RORγt agonist (8-074), which showed strong antitumor efficacy in a syngeneic tumor model and improved anti-PD-1 in mouse lung cancer.

The team took the lead in revealing the innovative pharmacological mechanism of RORγt agonists combined with immune checkpoint inhibitors, providing a theoretical basis for patient screening in clinical trials and new ideas for clinical tumor immunotherapy

In conclusion, RORγt agonists have a new mechanism for regulating the tumor immune microenvironment, that is, on the basis of enhancing the function of Type17 to promote the infiltration of CD8+ T cells and other immune cells, it can also improve immunity by reducing the proportion of immunosuppressive cells Treg.

about the author:

Xia Li, a doctoral student at the School of Pharmacy, Fudan University, and Tian Enming, a master's student, are the co-first authors

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