he balancing act that is cancer immunotherapy requires that the body’s antitumor response be given a boost, but not too much of a boost. For example, simply getting rid of Tregs, the regulatory T cells that moderate the immune system’s attack on cancer, would be risky. Such a rash act might precipitate a dangerous autoimmune reaction. An alternative, less extreme approach would be to inhibit Tregs while keeping them around.
Merely tinkering with Tregs, Columbia University researchers suspected, could boost cancer immunotherapy without letting the immune system get out of control. When the researchers tested the idea, by using a drug that interferes with Treg transcription, they found that standard checkpoint-blockade immunotherapies became more effective in mouse models.
Details of this work appeared September 7 in the journal Cell, in an article entitled, “NF-κB c-Rel Is Crucial for the Regulatory T Cell Immune Checkpoint in Cancer.” In this article, the Columbia University scientists report that NF-κB c-Rel ablation specifically impairs the generation and maintenance of the activated Treg (aTreg) subset, which is known to be enriched at sites of tumors.
“Using mouse models, we demonstrate that melanoma growth is drastically reduced in mice lacking c-Rel, but not p65, in Tregs,” the article’s authors wrote. “Moreover, chemical inhibition of c-Rel function delayed melanoma growth by impairing aTreg-mediated immunosuppression and potentiated the effects of anti-PD-1 immunotherapy.”
