Unlocking Melanoma Immunotherapy Resistance: New Clues from T-Cell Plasticity
Source: Inside Precision Medicine, April 2025
A new study offers clues to overcoming one of the most stubborn challenges in cancer treatment: resistance to immunotherapy. By examining both mouse models and clinical data from melanoma patients, the research team from Memorial Sloan Kettering Cancer Center (MSKCC) and the Earle A. Chiles Research Institute in Oregon has uncovered immune signatures that may help predict who will respond to a new combination immunotherapy—and why.
The research, published in Science Translational Medicine, centers on a combination of anti-PD-1 and anti-LAG-3 antibodies—two types of immune checkpoint inhibitors that aim to rev up the immune system’s attack on tumors. These therapies target proteins used by tumor cells to suppress T-cell activity. When successful, they unleash the immune system’s full anticancer potential. Yet despite their promise, immune checkpoint inhibitors don’t work for everyone. Many patients initially respond to anti-PD-1 drugs like nivolumab, only to become resistant over time.
“Immuno-oncology has given us some of the most powerful treatments in cancer,” said co-senior author Margaret Callahan, MD, PhD, of MSKCC. “But we’re still pretty bad at predicting which patients will respond to which therapies. That’s the real problem we set out to tackle.”