Mayo Clinic researchers have discovered that a potential marker called Bim may be a clue to overall survival in patients undergoing anti-PD-1 therapy.
The team believes that measuring the Bim protien in metastatic melanoma patients, may constitute a less invasive strategy for clinicians to identify patients less likely to benefit from such therapies. The study, “T cell Bim levels reflect responses to anti–PD-1 cancer therapy,” was published in the May 5 edition of JCI Insight.
PD-1 blockade immunotherapy targets the interaction between two molecules, PD-1 (programmed death 1 receptor) and PD-L1 (PD-1 ligand), expressed at the surface of T-cells and tumors. 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. To increase the anti-tumor immune response, researchers have made a considerable effort to develop several therapeutic molecules targeting PD-1, which have had varying degrees of success when it comes to patient response.
Because the therapy comes with significant side-effects and costs, researchers agree it is critically important to discover markers that can help predict the outcome of such approaches and deliver the more personalized clinical treatment to patients most likely to benefit from PD-1 blockage.
Mayo clinic researchers had previously demonstrated that PD-L1 is responsible for the upregulation of Bim in activated CD8+ T cells in tests performed in subjects. Next, they investigated if an increased frequency of T cells expressing Bim in patients who respond to immunotherapy reflects an increased number of target T cells for PD-1 blockade with pembrolizumab, explaining the improved outcomes in patients. By analyzing peripheral blood samples collected at initiation of treatment and 12 weeks after, PD-1 blockade response was 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 affecting clinical decision making and formulation of the most appropriate course of treatment.
“A great advantage of this approach lies in the ease of serial peripheral blood testing, compared with repeated invasive tissue biopsies,” lead author Dr. Roxana Dronca, said in a press release. “We are currently validating these results in a larger prospective cohort of patients with metastatic melanoma and in patients with lung cancer using multiple serial peripheral blood samples and standardized tumor assessment.”