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A Model for Perineural Invasion in Head and Neck Squamous Cell Carcinoma
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Immunogenomic correlates of response to cetuximab monotherapy in head and neck squamous cell carcinoma

Daniel L Faden1,2, Fernando Concha-Benavente3,4, Anish B Chakka5

  • 1Department of Otolaryngology, Division of Head and Neck Surgical Oncology, Massachusetts Eye and Ear Infirmary, Boston, Massachusetts.

Head & Neck
|March 5, 2019
PubMed
Abstract

Insights

Mutations in HLA-C genes may help head and neck squamous cell carcinoma (HNSCC) evade immune attack from epidermal growth factor receptor-specific antibody therapy. Blocking KIR in natural killer (NK) cells enhanced tumor cell killing.

Area of Science:

  • Immunology
  • Oncology
  • Genetics

Background:

  • Mechanisms of resistance to immune-modulating cancer therapies remain unclear.
  • This study investigates immune escape from epidermal growth factor receptor-specific monoclonal antibody (mAb) therapy in head and neck squamous cell carcinoma (HNSCC).

Purpose of the Study:

  • To explore the mechanisms of immune escape in HNSCC patients treated with cetuximab.
  • To identify genetic alterations associated with resistance to immune-modulating therapies.

Main Methods:

  • Whole-exome sequencing of HNSCC tumors (n=20) from patients receiving neoadjuvant cetuximab.
  • Assessment of killer-cell immunoglobulin-like receptor (KIR) and human leukocyte antigen-C (HLA-C) expression in HNSCC cell lines.
  • Evaluation of KIR blockade effects on natural killer (NK) cell activity against HNSCC cells.

Main Results:

  • Nonresponders exhibited significantly higher rates of HLA-C mutations compared to responders and The Cancer Genome Atlas HNSCC cohort (P < 0.00001).
  • Cetuximab-activated NK cells induced HLA-C upregulation on HNSCC cells via interferon gamma (P < 0.01).
  • Treatment with anti-KIR mAb lirilumab enhanced NK cell-mediated killing of HNSCC cells (P < 0.001).

Conclusions:

  • Alterations in HLA-C are implicated as a mechanism of immune evasion in HNSCC.
  • Disruption of NK cell activation through HLA-C modifications may contribute to treatment resistance.
  • Targeting KIR offers a potential strategy to overcome immune escape in HNSCC.
Keywords:
HLANK cellscetuximabhead and neck cancerimmunogenomics

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