Immune checkpoint blockade medications have revolutionized cancer treatment, giving patients and providers new hope to control and sometimes cure metastatic cancer. However, predicting which patients will benefit from this expensive and sometimes toxic, but potentially lifesaving, class of medications has been a challenge.

Now, UConn School of Medicine’s Dr. Margaret Callahan, chief of the Division of Hematology/Oncology at the Neag Comprehensive Cancer Center, and co-researchers show in Science Translational Medicine how a new mechanistic understanding of a specific immunotherapy combination may help guide future treatment decisions to match the right patient with the right therapy for them.

The research team first demonstrated that a combination of immune checkpoint-blocking antibodies, anti-PD-1 plus anti-LAG-3, can effectively influence a specific population of immune cells called regulatory T cells, known as Tregs, to make them less able to regulate the immune system. Then, a large clinical trial of metastatic melanoma patients receiving the drug combination of anti-PD-1 plus anti-LAG-3 also benefitted from the combination therapy and experienced the same changes in their Tregs.

Callahan says, “Together, our laboratory and human studies both show Tregs play a key, beneficial role for this drug combination and may serve as a biomarker to identify which patients will respond optimally.”