Loss of cancer cell STAT1 improves response to radiation therapy and promotes T cell activation in head and neck squamous cell carcinoma

Author(s):  
Michael W. Knitz ◽  
Laurel B. Darragh ◽  
Thomas E. Bickett ◽  
Shilpa Bhatia ◽  
Sanjana Bukkapatnam ◽  
...  
2020 ◽  
Vol 153 (5) ◽  
pp. 618-629
Author(s):  
Hao Li ◽  
Lei-Lei Yang ◽  
Cong-Cong Wu ◽  
Yao Xiao ◽  
Liang Mao ◽  
...  

Abstract Objectives Interferon-induced protein with tetratricopeptide repeats 1 (IFIT1) and interferon-induced transmembrane protein 3 (IFITM3) are commonly induced by type I interferon. The study aims to investigate the expression and clinical significance of IFIT1 and IFITM3 in head and neck squamous cell carcinoma (HNSCC). Methods Immunohistochemistry was applied on tissue microarray to reveal IFIT1 and IFITM3 expression in 275 HNSCC, 69 dysplasia, and 42 normal mucosa samples. The clinicopathologic features associated with IFIT1 and IFITM3 expression in HNSCC patients were analyzed. Results IFIT1 and IFITM3 were highly expressed in HNSCC tissues. High expression of IFIT1 and IFITM3 predicts a negative prognosis for patients (P < .01). IFIT1 and IFITM3 expression was associated with programmed cell death ligand 1, B7-H4, V-domain Ig suppressor of T-cell activation, indoleamine 2,3-dioxygenase, and macrophage marker immunoreactivity. Conclusions IFIT1 and IFITM3 were overexpressed in HNSCC and indicated poor prognoses for patients with HNSCC. IFIT1 and IFITM3 expression was correlated with several immune checkpoint molecules and tumor-associated macrophage markers.


2018 ◽  
Vol 18 (3) ◽  
pp. 182-191 ◽  
Author(s):  
Linda L. Eastham ◽  
Candace M. Howard ◽  
Premalatha Balachandran ◽  
David S. Pasco ◽  
Pier Paolo Claudio

Enthusiasm for the use of dietary bioactive compounds as chemopreventive agents and adjuvants for current therapies has increased laboratory research conducted on several types of cancers including Head and Neck Squamous Cell Carcinoma (HNSCC). The green chemoprevention movement is a modern approach to highlight healthy lifestyle changes that aim to decrease the incidence of HNSCC. A healthy diet can be an effective way to prevent the development of oral cancers. Discovery of the naturally occurring plant based compounds called phytochemicals has facilitated the development of new treatment strategies for patients that are at risk for, or have developed HNSCC. Many of these compounds have been shown to elicit very potent anti-carcinogenic properties. While there are many compounds that have been studied, the compounds from two specific categories of phytochemicals, phenolics (resveratrol, EGCG, curcumin, quercetin, and honokiol) and glucosinolates (sulforaphane, PEITC and BITC), are emerging as potent and effective inhibitors of oral carcinogenesis. These compounds have been shown to inhibit HNSCC growth through a variety of mechanisms. Research has demonstrated that these compounds can regulate cancer cell proliferation through the regulation of multiple cell signaling pathways. They can impede cell cycle progression, induce differentiation and apoptosis, prevent angiogenesis, and inhibit cancer cell invasive and metastatic properties. They can protect normal cells during treatment and reduce the damage caused by chemotherapy and radiotherapy. This review aims to provide an overview of some of the most effective phytochemicals that have the potential to successfully prevent and treat head and neck squamous cell carcinoma.


2020 ◽  
Vol 10 (1) ◽  
pp. 1856545
Author(s):  
Ryusuke Hayashi ◽  
Toshihiro Nagato ◽  
Takumi Kumai ◽  
Kenzo Ohara ◽  
Mizuho Ohara ◽  
...  

2018 ◽  
Author(s):  
Neeraja M Krishnan ◽  
Hiroto Katoh ◽  
Vinayak Palve ◽  
Manisha Pareek ◽  
Reiko Sato ◽  
...  

AbstractTumor suppression by the extracts of Azadirachta indica (neem) works via anti-proliferation, cell cycle arrest, and apoptosis, demonstrated previously using cancer cell lines and live animal models. However, very little is known about the molecular targets and pathways that the neem extracts and the associated compounds act through. Here, we address this using a genome-wide functional pooled shRNA screen on head and neck squamous cell carcinoma cell line treated with crude neem leaf extracts, known for their anti-tumorigenic activity. By analyzing differences in global clonal sizes of the shRNA-infected cells cultured under no treatment and treatment with neem leaf extract conditions, assayed using next-generation sequencing, we found 225 genes affected the cancer cell growth in the shRNA-infected cells treated with neem extract. Pathway enrichment analyses of whole-genome gene expression data from cells temporally treated with neem extract revealed important roles played by the TGF-β pathway and HSF-1-related gene network. Our results indicate that neem extract simultaneously affects various important molecular signaling pathways in head and neck cancer cells, some of which may be therapeutic targets for this devastating tumor.


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