Published in the Journal of Immunotherapy for Cancer: Single-Cell Analysis Demonstrates Biological Mechanism of NK Cell Cytotoxicity After Treatment of Solid Tumors with Metformin

Head and neck squamous cell carcinoma (HNSCC) is a common malignancy that have a high rate of recurrence, requiring more efficacious therapies to improve clinical outcomes. Metformin is an FDA-approved drug currently indicated for the treatment of type II diabetes and polycystic ovary disease, but recent studies have shown that metformin has potential as an anticancer therapeutic agent.

Metformin targets the mTOR pathway, which is upregulated in cancer cells, but can also directly affect immune cell function and maturation. Recent studies have shown that metformin plays a role in maintaining the activity of tumor infiltrating lymphocytes (TILs), but there is little data regarding how metformin affects the circulating peripheral blood mononuclear cells (PBMCs) that migrate to the tumor site upon antigen stimulation. Understanding the interaction between therapies and immune cells is vital for developing more effective anti-cancer treatments, but characterizing immune cell function using bulk analysis methods can miss key differences between individual cells in a heterogeneous population. Single-cell functional analysis, however, can measure the array of cytokines produced by individual cells within a population, giving a more complete picture of immune response.

Single-Cell Secretome Reveals Mechanisms of Metformin Treatment Response

In a paper recently published in the Journal of Immunotherapy for Cancer, researchers characterized immune cells from HNSCC donors and how metformin affected their function. The number of NK cells has been previously shown to be associated with cancer outcomes, so the researchers decided to focus on NK cell frequency and function. As expected, HNSCC donors had fewer circulating NK and NKT cells compared to healthy controls. However, the researchers found that metformin treatment increased NK cell infiltration into tumors.

To investigate this further, the researchers used IsoPlexis’ Single-Cell Secretome solution to characterize how metformin affected NK cell cytokine release. NK cells isolated from PBMCs of newly diagnosed HNSCC donors were treated with either metformin or vehicle before being loaded onto IsoCode chips for multiplexed analysis of the single-cell secretome. When the secreted cytokines were analyzed, the researchers found that metformin treatment significantly increased the secretion of perforin, a cytotoxic molecule. The researchers also found that metformin decreased cytokines known to be tumorigenic, such as IL-6, IL-8, IL-9, and IL-10. These results helped to provide a potential mechanism for how metformin affects NK cell cytotoxicity and can be used to develop more effective therapies to treat solid tumors.

Uncovering Mechanisms of Anti-Cancer Activity with IsoPlexis’ Single-Cell Analysis

By performing multiplexed analysis of individual cell secretions, researchers can identify how therapies alter cell function and can gain insight into molecular mechanisms of therapeutic response. By understanding how therapies drive immune cell responses, researchers can develop more effective therapies and improve treatment of solid tumors. IsoPlexis’ Single-Cell Secretome solution gives researchers a platform to better understand cell function at the single-cell level, accelerating research and enabling breakthroughs.

 

Learn more about how IsoPlexis’ Single-Cell Secretome platform is revealing key insights into NK cells in this application note: IsoPlexis Proteomic Product Suite for NK Cells | IsoPlexis

NK Cell App Note

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