Successful Outcome of PD-1 Immunotherapy for Melanoma May Be Predicted By New Protein Marker

Source: Immuno-Oncology News, September 2015

A new study conducted by Mayo Clinic researchers, and recently presented at the American Association for Cancer Research International Cancer Immunotherapy Conference in New York City, highlights the correlation between the presence of a protein marker (Bim) and PD-1 blockade therapy, which may predict treatment success.

PD-1 blockade immunotherapy targets the interaction between two molecules, PD-1 (programmed death 1 receptor) expressed at T-cell surface and PD-L1 (PD-1 ligand). This interaction ultimately leads to T cell death. T cells are an important subset of immune cells that recognize and eliminate cancer cells. Up regulation of PD-L1 is one of the mechanisms by which different cancer types can limit and evade the host immune response, decreasing T cell population and leading to cancer cell survival and proliferation. In order to increase the immune anti-tumor response, researchers have made a considerable effort to develop several therapeutical molecules targeting PD-1, all of which have had varying degrees of success when it comes to patient response.

As a result, researchers agree that it is critically important to discover markers that can help predict the outcome of these types of therapeutic approaches and deliver a more personalized clinical treatment by identifying patients who are more likely to benefit from PD-1 blockage. Roxana Dronca, M.D., lead author of the abstract, notes that this effort ultimately benefits the patient’s well-being: “This will allow us to expose fewer patients to inadequate treatments, and their associated toxicities and costs.”

The study conducted by Mayo researchers focused on the response of metastatic melanoma patients to pembrolizumab, an anti-PD-1 drug, and the correlation between these patients’ responses to the marker Bim, a protein activated by PD-1:PD-L1 interaction and involved in T cell death induction. The findings reveal that PD-1 blockade response is proportional to the presence of T cells expressing Bim and PD-1. Assessing the level of these cells in a patient’s blood prior to therapy could be a factor when deciding if PD-1 blockade is the best course of treatment. The researchers also observed that higher levels of soluble PD-L1 in the blood were correlated with a more effective patient response.

This study further highlighted the importance of PD-1: PD-L1 interaction in cancer proliferation and also in the response to PD-1 blockade therapy.

https://youtu.be/ava8Q6n_Y8o