The Emerging Role of Exosomes in Diagnosis, Prognosis, and Therapy in Head and Neck Cancer

Exosomes, the smallest group of extracellular vesicles, carry proteins, miRNA, mRNA, DNA, and lipids, which they efficiently deliver to recipient cells, generating a communication network. Exosomes strongly contribute to the immune suppressive tumor microenvironment of head and neck squamous cell carcinomas (HNSCC). Isolation of exosomes from HNSCC cell culture or patient’s plasma allows for analyzing their molecular cargo and functional role in immune suppression and tumor progression. Immune affinity-based separation of different exosome subsets, such as tumor-derived or T cell-derived exosomes, from patient’s plasma simultaneously informs about tumor status and immune dysfunction. In this review, we discuss the recent understanding of how exosomes behave in the HNSCC tumor microenvironment and why they are promising liquid biomarkers for diagnosis, prognosis, and therapy in HNSCC.

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Tumor microenvironment and immune evasion in head and neck squamous cell carcinoma

International Journal of Oral Science ◽

10.1038/s41368-021-00131-7 ◽

2021 ◽

Vol 13 (1) ◽

Author(s):

Areeg Elmusrati ◽

Justin Wang ◽

Cun-Yu Wang

Keyword(s):

Squamous Cell Carcinoma ◽

Immune System ◽

Tumor Microenvironment ◽

Cell Carcinoma ◽

Head And Neck ◽

Squamous Cell ◽

Neck Squamous Cell Carcinoma ◽

High Morbidity ◽

Advanced Therapies

AbstractHead and neck squamous cell carcinoma (HNSCC), an aggressive malignancy, is characterized by high morbidity and low survival rates with limited therapeutic options outside of regional surgery, conventional cytotoxic chemotherapy, and irradiation. Increasing studies have supported the synergistic role of the tumor microenvironment (TME) in cancer advancement. The immune system, in particular, plays a key role in surveillance against the initiation, development, and progression of HNSCC. The understanding of how neoplastic cells evolve and evade the immune system whether through self-immunogenicity manipulation, or expression of immunosuppressive mediators, provides the foundation for the development of advanced therapies. Furthermore, the crosstalk between cancer cells and the host immune system have a detrimental effect on the TME promoting angiogenesis, proliferation, and metastasis. This review provides a recent insight into the role of the key inflammatory cells infiltrating the TME, with a focus on reviewing immunological principles related to HNSCC, as cancer immunosurveillance and immune escape, including a brief overview of current immunotherapeutic strategies and ongoing clinical trials.

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Tumor Microenvironment in Head and Neck Squamous Cell Carcinomas

Turk Otolarengoloji Arsivi/Turkish Archives of Otolaryngology ◽

10.5152/tao.2015.1065 ◽

2015 ◽

Vol 53 (3) ◽

pp. 120-127 ◽

Cited By ~ 3

Author(s):

Gorkem Eskiizmir

Keyword(s):

Tumor Microenvironment ◽

Head And Neck ◽

Squamous Cell ◽

Squamous Cell Carcinomas

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The Functional Role of Dried Fig, Date and Olive Oil on Rats with Immune Dysfunction

Journal of Food and Dairy Sciences ◽

10.21608/jfds.2018.36021 ◽

2018 ◽

Vol 9 (9) ◽

pp. 313-320

Author(s):

Hoda Ibrahim ◽

N. Rabeh ◽

Hanan Elghandour ◽

Shafika Sabry

Keyword(s):

Olive Oil ◽

Functional Role ◽

Immune Dysfunction

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The complex role of EZH2 in the tumor microenvironment: opportunities and challenges for immunotherapy combinations

Future Medicinal Chemistry ◽

10.4155/fmc-2020-0072 ◽

2020 ◽

Vol 12 (15) ◽

pp. 1415-1430

Author(s):

Jing Qiu ◽

Shikhar Sharma ◽

Robert A Rollins ◽

Thomas A Paul

Keyword(s):

Tumor Microenvironment ◽

Cell Fate ◽

Cell Function ◽

Immune Dysfunction ◽

Lymphoid Cells ◽

Epigenetic Changes ◽

Immune Effector ◽

Effector Functions ◽

Tumor Immunogenicity

Immune dysfunction in the tumor microenvironment occurs through epigenetic changes in both tumor cells and immune cells that alter transcriptional programs driving cell fate and cell function. Oncogenic activation of the histone methyltransferase EZH2 mediates gene expression changes, governing tumor immunogenicity as well as differentiation, survival and activation states of immune lineages. Emerging preclinical studies have highlighted the potential for EZH2 inhibitors to reverse epigenetic immune suppression in tumors and combine with immune checkpoint therapies. However, EZH2 activity is essential for the development of lymphoid cells, performing critical immune effector functions within tumors. In this review, we highlight the complexity of EZH2 function in immune regulation which may impact the implementation of combination with immunotherapy agents in clinic.

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51. Role of biomarkers in prognosis and treatment of head and neck squamous cell carcinomas

Pathology ◽

10.1016/s0031-3025(16)33339-6 ◽

2011 ◽

Vol 43 ◽

pp. S105

Author(s):

A. Thomas ◽

P. Friedland ◽

A. Naran ◽

B. Amanuel ◽

F-G. Iacopetta ◽

...

Keyword(s):

Head And Neck ◽

Squamous Cell ◽

Squamous Cell Carcinomas

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A Critical Role of c-Cbl-Interacting Protein of 85 kDa in the Development and Progression of Head and Neck Squamous Cell Carcinomas through the Ras-ERK Pathway

Neoplasia ◽

10.1593/neo.10396 ◽

2010 ◽

Vol 12 (10) ◽

pp. 789-IN4 ◽

Cited By ~ 22

Author(s):

Takahiro Wakasaki ◽

Muneyuki Masuda ◽

Hiroaki Niiro ◽

Siamak Jabbarzadeh-Tabrizi ◽

Kumiko Noda ◽

...

Keyword(s):

Head And Neck ◽

Squamous Cell ◽

Critical Role ◽

Squamous Cell Carcinomas ◽

Erk Pathway ◽

Interacting Protein

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Fascin is a circulating tumor marker for head and neck cancer as determined by a proteomic analysis of interstitial fluid from the tumor microenvironment

Clinical Chemistry and Laboratory Medicine (CCLM) ◽

10.1515/cclm-2014-1016 ◽

2015 ◽

Vol 53 (10) ◽

Cited By ~ 8

Author(s):

Li-Yu Lee ◽

Yin-Ju Chen ◽

Ya-Ching Lu ◽

Chun-Ta Liao ◽

I-How Chen ◽

...

Keyword(s):

Cell Culture ◽

Head And Neck Cancer ◽

Tumor Microenvironment ◽

Head And Neck ◽

Cancer Patients ◽

Tumor Markers ◽

Interstitial Fluid ◽

Culture Supernatant ◽

Cell Culture Supernatant ◽

Cancer Tissues

AbstractHead and neck cancer (HNC) is a prevalent cancer worldwide; however, clinically useful tumor markers for HNC have not been identified. Here, we aimed to identify secretory proteins from the tumor microenvironment as candidate circulating tumor markers.Samples derived from seven pairs of tumor interstitial fluid (TIF) and normal interstitial fluid (NIF) samples from patients with HNC were analyzed. The proteomes were determined by gel-based-mass-spectrometry proteomic methods. The most up-regulated protein, fascin was confirmed in the cancer tissues and cell culture supernatant by immunoblotting and immunohistochemistry assays. Serum fascin was determined in 40 HNC and 40 normal individuals by ELISA.After proteomics analysis, 189 peptides were identified, corresponding to 75 proteins. Of the 21 proteins which were identified more than twice, five up-regulated proteins identified most frequently including fascin. The most elevated fascin was over-expressed in cancer tissues and cell culture supernatant. Serum fascin was significantly up-regulated in the cancer patients (p<0.001) and correlated with pathological lymph node metastasis (p=0.022). To assess the diagnostic efficacy, serum levels of fascin and another potential biomarker SCCA were determined. Fascin showed a high predictable value with an area under the curve (AUC) of 0.808 (95% CI 0.723–0.901) in the receiver operator curve (ROC), compared to 0.501 (95% CI 0.378–0.634) for SCCA.We have identified 75 potential circulating tumor markers associated with HNC, including fascin. Serum fascin could discriminate cancer patients from healthy individuals; thus, it may serve as a circulating biomarker for HNC.

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