Metformin Plus Chemoradiation Induces Antitumorigenic Immune Response in HNSCC

Vidhya Karivedu, MD, fellow/resident at the University of Cincinnati College of Medicine, discusses the antitumorigenic immune response seen with the combination of metformin and chemoradiation in patients with locally advanced head and neck squamous cell carcinoma (HNSCC).

Preclinical data have shown that metformin inhibits tumor growth and proliferation in several cancers, including HNSCC, says Karivedu. Due to the agent’s mechanism of action, it was hypothesized to affect the immune regulation in the tumor microenvironment which would then lead to increased tumor cell death, she explains.

In a phase I open-label, single-site dose escalation trial (NCT02325401), investigators evaluated the combination of metformin and chemoradiation in patients with HNSCC. Results presented at the 2018 ASCO Annual Meeting showed an increase in overall survival (OS) with the combination. Specifically, at 2 years, overall survival increased to 90%, says Karivedu.

Based on that data, Karivedu and her team set out to explore the immune cell phenotypes and cytokine profiles of peripheral blood in the patients enrolled in the trial, both before and after they received metformin through the use of flow cytometry and cytokine magnetic bead assays.

Patients treated with metformin and chemoradiation expressed a greater presence of antitumorigenic cytokines, specifically IL-2 and TNF-α, says Karivedu. In contrast, there was a lower presence of protumorigenic cytokines like IL-6 in these patients. A shift in CD8-positive memory T cells was also observed, along with greater natural killer cell activity and increased expression of the activating receptor cell NKG2D, she adds.

Based on these observations, Karivedu concludes that metformin continues to be a good candidate for the treatment of patients with advanced-stage HNSCC.