Bruker Cellular Analysis / Blog / Cancer Immunology / Published in Head & Neck: Cytokine Profiling Reveals How Novel Kinase Inhibitor Slows Tumor Cell Growth by Altering Tumor Microenvironment

Published in Head & Neck: Cytokine Profiling Reveals How Novel Kinase Inhibitor Slows Tumor Cell Growth by Altering Tumor Microenvironment

Blog Post_Cytokine Profiling Reveals How Novel Kinase Inhibitor Slows Tumor Cell Growth_jt

Every year, head and neck cancers (HNC) claim thousands of lives, with over 54,000 cases diagnosed annually in the United States alone, resulting in approximately 11,000 fatalities.1 HNCs are particularly difficult to treat—about one in three patients will not survive five years after diagnosis, despite a range of treatment options including surgery, radiation, chemotherapy, and newly approved immune checkpoint inhibitors (ICIs).1

A major challenge in treating HNCs is that they are only 15% likely to respond to initial ICI treatment.2 This relatively low response rate is largely due to a “cold” tumor microenvironment (TIME), characterized by lack of T cell infiltration and overexpression of the tyrosine kinase receptors Axl and MerTK. When overexpressed, Axl and MerTK help polarize macrophages (a type of immune cell) from their M1 antitumor phenotype to their M2 protumor phenotype. This shift from M1 to M2 promotes tumor growth and progression, making cancers with a cold TIME difficult to treat with ICIs.

In contrast, cancers with “hot” TIMEs demonstrate high levels of T cell and other proinflammatory cell infiltration. As a result, they are more likely to respond to ICIs, including anti-PDL1 treatments. Developing therapeutics that can switch the TIME from cold to hot in HNC may help develop more effective ICIs for this complex and heterogenous cancer.

Analyzing How Axl/MerTK Inhibition Promotes a “Hot” Antitumor Microenvironment

In a recent study published in Head & Neck, researchers tested whether inhibiting Axl/MerTK receptors could create a hotter TIME by promoting M1 polarization and preventing M2 polarization in mouse oral cancer cells (MOC). To test this hypothesis, they treated MOC cells with either 6 μM of a novel kinase inhibitor (INCB081776) that suppresses Axl/MerTK expression, or a control substance. Then, both groups were treated with 18 ng/mL Gas6, a protein that binds to Axl/MerTKPu receptors and activates cellular processes that could promote tumor growth.

To measure cytokine activity in response to Axl/MerTK inhibition, researchers used Bruker Cellular Analysis’ CodePlex Secretome chips (Mouse Inflammation panel). This tool enabled researchers to assess the secretion of protumor cytokines such as TNFα, GMCSF, IL-1β, and MCP-1.

Data from CodePlex Secretome chips and other tools supported the hypothesis that INCB081776 treatment in mouse HNC cells created a hotter TIME by decreasing levels of protumor GMCSF and MCP-1 cytokines and increasing the M1/M2 ratio.

Researchers also combined INCB081776 treatment with standard-of-care immune checkpoint inhibitor targeting PDL1. They found that the combination of two therapies created a hotter TIME and slow tumor growth more than either treatment alone. These findings suggest that altering TIMEs with INCB081776 treatment could enhance the efficacy of ICIs for patients with HNC.

Powering Cytokine Profiling to Harness Tumor Microenvironments Against Cancer

Additional research will be needed to inform better ICI treatment regimens for HNC and other cancers with cold TIMEs. Accurate and efficient cytokine profiling tools will enable future research with cost-effective, streamlined workflows and powerful analysis.

Bruker Cellular Analysis’ CodePlex Secretome chips support a variety of mouse and human functional immune profiling panels to help researchers optimize experimental conditions. CodePlex chips can assess up to 22 different cytokines at once in a fully automated workflow, helping to accelerate research that may ultimately prove to improve treatment outcomes in HNC and other cancers.

Learn more here:  Bruker Cellular Analysis’ CodePlex solution

  1. Siegel RL, Miller KD, Fuchs HE, Jemal A. Cancer statistics, CA Cancer J Clin. 2022;72:7-33.
  2. Whiteside, TL. Head and neck carcinoma immunotherapy: facts and h Clin. Cancer Res. 2018;24(1), 6-13.
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