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- W2919934319 abstract "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." @default.
- W2919934319 created "2019-03-11" @default.
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- W2919934319 date "2019-03-04" @default.
- W2919934319 modified "2023-10-16" @default.
- W2919934319 title "Immunogenomic correlates of response to cetuximab monotherapy in head and neck squamous cell carcinoma" @default.
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- W2919934319 doi "https://doi.org/10.1002/hed.25726" @default.
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