Premium
Immunogenomic correlates of response to cetuximab monotherapy in head and neck squamous cell carcinoma
Author(s) -
Faden Daniel L.,
ConchaBenavente Fernando,
Chakka Anish B.,
McMichael Elizabeth L.,
Chandran Uma,
Ferris Robert L.
Publication year - 2019
Publication title -
head and neck
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.012
H-Index - 127
eISSN - 1097-0347
pISSN - 1043-3074
DOI - 10.1002/hed.25726
Subject(s) - cetuximab , head and neck squamous cell carcinoma , medicine , cancer research , immune system , epidermal growth factor receptor , head and neck cancer , immunotherapy , antibody , monoclonal antibody , immunology , cancer , oncology
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.