The Bim protein might predict which patients could be successfully treated with immunotherapy for metastatic melanoma.1

PD-1 blockade is an immunotherapy that enables the body’s own immune cells to attack cancer cells by blocking the activity of PD-1, which inhibits T cells in the immune system from recognizing tumors. Pembrolizumab acts via a PD-1 blockade.1

“Immune checkpoint therapy with PD-1 blockade has emerged as an effective treatment for many advanced cancers,” said Roxana Dronca, MD, an oncologist at the Mayo Clinic, Rochester, Minnesota, and first author of the study.

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“However, only a fraction of patients achieve durable responses to immunotherapy and, to date, we have had no means of predicting which patients are most likely to benefit.”

This study, published in JCI Insight, revealed a higher frequency of T cells with Bim protein in patients with metastatic melanoma who responded to pembrolizumab than in patients whose disease progressed even with pembrolizumab treatment.

“Our previous research demonstrated that Bim is a downstream signaling molecule in the PD-1 signaling pathway, and that levels of Bim reflect the degree of PD-1 interaction with its ligand PD-L1,” said Haidong Dong, MD, PhD, associate professor of immunology at the Mayo Clinic, and the study leader.

Researchers collected peripheral blood from patients at the beginning of pembrolizumab treatment and at 12 weeks, which was the time of first radiographic tumor assessment. Samples were then collected at each subsequent radiographic tumor evaluation for patients who continued receiving pembrolizumab.

This study revealed that high levels of Bim protein in T cells correlated with poor survival when patients with metastatic melanoma did not receive anti-PD-1 therapy and with clinical benefit when patients were treated with anti-PD-1 therapy.

“A great advantage of this approach lies in the ease of serial peripheral blood testing, compared with repeated invasive tissue biopsies,” said Dronca.

“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.”


1. Dronca RS, Liu X, Harrington SM, et al. T cell Bim levels reflect responses to anti-PD-1 cancer therapy [published online ahead of print May 5, 2016]. JCI Insight. doi:10.1172/jci.insight.86014DS1.