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MYC-PDL1 axis reduces sensitivity to nivolumab in recurrent head and neck squamous cell carcinoma

Rika Noji1, Yoshihito Kano2, Hideaki Hirai3

  • 1Department of Precision Cancer Medicine, Center for Innovative Cancer Treatment, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-Ku, Tokyo 113-8510, Japan; Department of Oral and Maxillofacial Surgery, Division of Oral Health Sciences, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-Ku, Tokyo 113-8510, Japan.

Oral Oncology
|December 13, 2021
PubMed

Insights

In head and neck cancer, nivolumab showed varied responses in metastatic sites. MYC amplification and PD-1 loss in new metastases may predict resistance to immune checkpoint inhibitors (ICIs).

Area of Science:

  • Oncology
  • Immunotherapy
  • Genomics

Background:

  • Recurrent or metastatic squamous cell carcinoma of the head and neck (R/M HNSCC) has a poor prognosis.
  • Immune checkpoint inhibitors (ICIs) show promise but have low response rates, necessitating predictive biomarkers.
  • Identifying resistance mechanisms is crucial for optimizing ICI therapy.

Observation:

  • A patient with R/M HNSCC exhibited differential responses to nivolumab across metastatic lesions.
  • Cervical lymph node metastases significantly reduced, while a new axillary lymph node metastasis emerged.
  • Surgical specimens revealed distinct genetic profiles in responding versus non-responding metastases.

Findings:

  • Next-generation sequencing identified MYC amplification and programmed cell death-1 (PD-1) loss in the new axillary metastasis.
  • MYC amplification appeared to regulate programmed death-ligand 1 (PD-L1) expression.
  • These genetic alterations correlated with decreased response to ICIs.

Implications:

  • MYC amplification and PD-1 loss may serve as predictive biomarkers for ICI resistance in HNSCC.
  • Understanding these mechanisms can guide the selection of appropriate therapeutic agents.
  • This case highlights the importance of molecular profiling for personalized cancer treatment.

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