STING activation enhances cetuximab-mediated NK cell activation and DC maturation and correlates with HPV+ status in head and neck cancer.

Oral Oncology
Shanhong LuR L Ferris

Abstract

The intracellular DNA sensor stimulator of interferon genes (STING) has recently been shown to play a vital role in anti-viral and anti-tumor immune responses stimulating cytokine production. While human papillomavirus (HPV) is a causative agent for a subset of head and neck squamous cell carcinoma (HNSCC) with unique etiology and clinical outcome, how the STING pathway is regulated in a virus-induced tumor microenvironment is not well understood. Since STING inactivation likely reflects immunoescape via innate immunity, we hypothesized that its restoration would improve efficacy of the immune modulatory monoclonal antibody (mAb), cetuximab. We correlated STING protein expression with clinical parameters by immunohistochemistry (n = 106) and its mRNA expression from The Cancer Genome Atlas (TCGA) in HNSCC tissue specimens. STING protein expression was tested for association with cancer-specific survival (CSS). We further examined the impact of STING activation on cetuximab-mediated immunity using an in vitro NK:DC:tumor cells co-culture system. In this study, we found that expression of STING both at the protein and mRNA level was higher in HPV positive (HPV+) specimens but unrelated to TNM stage or cancer-specific survival. Ou...Continue Reading

Citations

Feb 23, 2020·Medicina·Aušra Stumbrytė-KaminskienėIrina Mackevičienė
Nov 5, 2019·Molecular Cancer·Yuanyuan ZhuXiaobo Li
Jun 11, 2020·Current Pharmaceutical Design·Yuanjin GongChongyou Zhang
Mar 1, 2019·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Sayuri MiyauchiAndrew B Sharabi
Nov 8, 2020·International Journal of Molecular Sciences·Xinyu QuKatie Meehan
Feb 20, 2020·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Yuanlin WuZhangang Xiao
Aug 7, 2021·Molecular Aspects of Medicine·Jiarong ZhouLiangfang Zhang
Apr 28, 2021·Cancer Research·Emma SaultersLekh N Dahal

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Methods Mentioned

BETA
ELISA
FACS
Assay
RNAseq
flow cytometry

Software Mentioned

FlowJo

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