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- Title
Immunogenomic correlates of response to cetuximab monotherapy in head and neck squamous cell carcinoma.
- Authors
Faden, Daniel L.; Concha‐Benavente, Fernando; Chakka, Anish B.; McMichael, Elizabeth L.; Chandran, Uma; Ferris, Robert L.
- Abstract
Background: Mechanisms of resistance to immune‐modulating cancer treatments are poorly understood. Using a novel cohort of patients with head and neck squamous cell carcinoma (HNSCC), we investigated mechanisms of immune escape from epidermal growth factor receptor‐specific monoclonal antibody (mAb) therapy. Methods: HNSCC tumors (n = 20) from a prospective trial of neoadjuvant cetuximab monotherapy underwent whole‐exome sequencing. Expression of killer‐cell immunoglobulin‐like receptor (KIR) and human leukocyte antigen‐C (HLA‐C) and the effect of KIR blockade were assessed in HNSCC cell lines. Results: Nonresponders to cetuximab had an increased rate of mutations in HLA‐C compared to responders and HNSCC tumors (n = 528) in The Cancer Genome Atlas (P < 0.00001). In vitro, cetuximab‐activated natural killer (NK) cells induced upregulation of HLA‐C on HNSCC cells (P < 0.01) via interferon gamma. Treatment of NK cells with the anti‐KIR mAb lirilumab increased killing of HNSCC cells (P < 0.001). Conclusions: Alterations in HLA‐C may provide a mechanism of immune evasion through disruption of NK activation.
- Subjects
SQUAMOUS cell carcinoma; EPIDERMAL growth factor; KILLER cells; INTERFERON gamma; THERAPEUTICS
- Publication
Head & Neck, 2019, Vol 41, Issue 8, p2591
- ISSN
1043-3074
- Publication type
Article
- DOI
10.1002/hed.25726