Discovery Could Predict Immunotherapy Response in Melanoma

A team of British researchers from King’s College London, Guy’s and St Thomas’ Hospital Trust and the Francis Crick Institute have discovered a rare type of immune cell that potentially predicts how likely it is certain patients with skin cancer will be responsive to treatment via immunotherapy. Specifically, they found that Vd1-gd T cells had the ability to recognize and kill cancer cells without identifying mutations, and can be found inside tumors where the immune checkpoint protein programmed cell death protein 1 (PD-1) is also present.

“The study findings may help doctors decide which patients are most likely to benefit from current immunotherapies,” stated co-first author Shraddha Kamdar, PhD, MSc, a research fellow at King’s College London. “These therapies are both costly and importantly can cause severe and lifelong side effects, so it is important to be able to predict when they will actually work.”

The findings were based on clinical trial data of 127 patients with melanoma who had been treated with PD-1-targeting immune checkpoint inhibitors, and this data revealed that Vd1-gd T cells’ presence could predict positive response to immunotherapy, especially in cancers with a low number of mutations. Researchers then grew cells from human tissue in a laboratory setting to illustrate that immune checkpoint inhibition therapy could reactivate Vd1-gd T cells, and learned that therapies utilizing Vd1-gd T cells could be effective for relatively longer than therapies using other types of T cells.

According to the National Cancer Institute, immune checkpoints, a standard element of a patient’s immune system, keep the body from destroying healthy cells and engage when proteins on the surface of T cells identify and bind to immune checkpoint proteins on cells such as tumor cells, and the bond between the checkpoint and the protein deactivates T cells. Immune checkpoint inhibitors block the binding of checkpoint and partner proteins, enabling the T cell to remain active and fight cancer cells.

Given the potential side effects associated with immunotherapy, including inflammation of the skin, intestines and liver, being able to predict which patients are likely to benefit from the treatment could be useful information for patients and their care teams.