ESMO Immuno-Oncology 2025 | Epigenetic drivers of innate immune signaling in head and neck cancer
Amanda Psyrri, MD, PhD, FACP, National Kapodistrian University of Athens, Athens, Greece, describes the impact of molecular mechanisms, such as epigenetic deregulation, on innate immune signaling, highlighting the role of NSD1 mutations and NSD2 upregulation in head and neck carcinoma. STING agonists have been explored to restore type 1 interferon signaling, and studies that have assessed the combination of pembrolizumab with STING agonists in PD-L1 positive tumors have shown durable responses. This interview took place at 2025 European Society for Medical Oncology (ESMO) Immuno-Oncology Congress in London, UK.
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Transcript
Besides IO combination, other molecular mechanisms such as epigenetic deregulation can influence innate immune signaling. So we know, for example, that NSD1 mutations are present in 8% of head and neck carcinoma. And patients with these mutations are hypermethylated and immunologically cold with low interferon activity. Also in HPV-positive tumors, NSD2 upregulation driven by E6 oncoproteins similarly yields to immune exclusion...
Besides IO combination, other molecular mechanisms such as epigenetic deregulation can influence innate immune signaling. So we know, for example, that NSD1 mutations are present in 8% of head and neck carcinoma. And patients with these mutations are hypermethylated and immunologically cold with low interferon activity. Also in HPV-positive tumors, NSD2 upregulation driven by E6 oncoproteins similarly yields to immune exclusion. So to restore the type 1 interferon signaling, STING agonists have been explored. In a study led by Fayette and colleagues, the combination of pembrolizumab with STING agonists in PD-L1 positive tumors resulted in responses in 54% of the patients, many of which were durable.
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