Immunotherapy has transformed the treatment of advanced melanoma, the deadliest form of skin cancer, by helping the immune system attack cancer cells. New combinations of immune checkpoint therapies have improved survival for many patients, but only about 30–60% experience lasting benefit. At the same time, these treatments can cause serious side effects and are extremely costly. Currently, doctors have no reliable way to predict which therapy is most likely to work for an individual patient, meaning treatment decisions are often based on trial and error.
Dr. Callahan seeks to solve that problem by developing blood-based biomarkers that can help guide treatment selection for patients with advanced melanoma. Her team has spent more than a decade studying how patients respond to immunotherapy and has already identified biomarkers linked to resistance to PD-1 therapy, one of the most widely used forms of immunotherapy. The team has also discovered a new biomarker related to the behavior of regulatory T cells, specialized immune cells that normally help control immune responses but can also suppress the body’s ability to fight cancer.
Successful treatment with the increasingly common combination therapy targeting PD-1 and LAG-3 may depend on shifting these regulatory T cells into a less suppressive, more active state. In this study, she will validate this biomarker in large groups of melanoma patients and investigate the biological mechanisms behind it. Her team will also combine this marker with other known predictors of response to create a more complete framework for personalized treatment decisions.
This work could help doctors match patients to the most effective immunotherapy while reducing unnecessary toxicity, improving outcomes, and making cancer care more precise and cost-effective.
Projects and Grants
Regulatory T cell programming is a key determinant of response to anti-PD-1+anti-LAG-3 therapy
