Immune Modulation of DUX4 in Cancer

Immune Modulation of DUX4 in Cancer

DUX4 as predictive biomarker and therapeutic target to enhance the effectiveness of immunotherapies

Although immune checkpoint blockade therapies represent important treatments for cancer, most patients are non-responders or may relapse. The efficacy of these treatments relies on cytotoxic T-cell recognition of antigens presented by MHC Class I on tumor cells and can be reduced by suppression of antigen presentation or blunt tumor-immune interactions. Fred Hutch researchers have discovered that DUX4, a double homeobox transcription factor expressed normally only early in development, is a novel regulator of antigen presentation and immune modulation. They found that DUX4 is re-expressed in solid tumors, is associated with anti-tumor activity, and promotes resistance to immune checkpoint blockade. Therefore, DUX4 is useful not only as a biomarker for identifying patients that may respond to immunotherapies, but also as a target to increase the effectiveness of immunotherapies.

<ul>

       <li>Therapeutic target for cancer treatment <li>

       <li>Therapeutic target to upregulate MHC Class 1 for use in combination with adoptive TCR-based T cell therapies<li>

       <li>Predictive biomarker for immunotherapy response <li>

</ul>

<ul>

       <li>Reveals a molecular basis for DUX4 amplification in cancer cells  </li>

</ul>

The global cancer therapeutics market was valued at USD 164 billion in 2022 and is estimated to grow at a CAGR of 9.2% during 2023- 2032. Main market drivers include increase in cancer prevalence, advances in cancer research and surge in collaboration between pharmaceutical companies.

<ul>
       <li>Stephen Tapscott, MD, PhD, Human Biology and Clinical Research Divisions, TDS IRC <li>
       <li>Robert Bradley, PhD, Basic Sciences and TDS IRC; Public Health Sciences Division; McIlwain Family Endowed Chair in Data Science<li>
</ul>

Preclinical <em>in vitro</em>

US20220202845A1

18-152_Bradley_Tapscott_DUX4 in cancer_FHCC_NCS.pdf

|Target | Immunotherapy | Dux4 |MHC Class 1

Immune-Modulation-DUX4-Cancer-18-152