Targeting the Immune Microenvironment in the Treatment of Head and Neck Squamous Cell Carcinoma

Wang, Hui‐Ching; Chan, Leong‐Perng; Cho, Shih‐Feng

doi:10.3389/fonc.2019.01084

Cited by 68 publications

(61 citation statements)

References 147 publications

(144 reference statements)

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“…RTKs: receptor tyrosine kinases. The tumor immune microenvironment (TIME) plays an important role in many tumors including HNSCC [100]. HNSCCs with YAP amplification and/or overexpression associate with resistance to the immunotherapy agent Pembrolizumab [94].…”

Section: The Hippo-yap Pathway In Hnsccmentioning

confidence: 99%

Hippo Pathway and YAP Signaling Alterations in Squamous Cancer of the Head and Neck

Santos-de-Frutos

Segrelles

Lorz

2019

JCM

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Head and neck cancer affects the upper aerodigestive tract and is the sixth leading cancer worldwide by incidence and the seventh by cause of death. Despite significant advances in surgery and chemotherapy, molecularly targeted therapeutic options for this type of cancer are scarce and long term survival rates remain low. Recently, comprehensive genomic studies have highlighted the most commonly altered genes and signaling pathways in this cancer. The Hippo-YAP pathway has been identified as a key oncogenic pathway in multiple tumors. Expression of genes controlled by the Hippo downstream transcriptional coactivators YAP (Yes-associated protein 1) and TAZ (WWTR1, WW domain containing transcription regulator 1) is widely deregulated in human cancer including head and neck squamous cell carcinoma (HNSCC). Interestingly, YAP/TAZ signaling might not be as essential for the normal homeostasis of adult tissues as for oncogenic growth, altogether making the pathway an amenable therapeutic target in cancer. Recent advances in the role of Hippo-YAP pathway in HNSCC have provided evidence that genetic alterations frequent in this type of cancer such as PIK3CA (phosphatidylinositide 3-kinase catalytic subunit alpha) overexpression or FAT1 (FAT atypical cadherin 1) functional loss can result in YAP activation. We discuss current therapeutic options targeting this pathway which are currently in use for other tumor types.

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Section: The Hippo-yap Pathway In Hnsccmentioning

confidence: 99%

Hippo Pathway and YAP Signaling Alterations in Squamous Cancer of the Head and Neck

Santos-de-Frutos

Segrelles

Lorz

2019

JCM

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“…These include systematic analysis of ligands by exponential enrichment (SELEX), RNA immunoprecipitation (RIP)-based methods, cross-linking immunoprecipitation (CLIP), RNA pulldown assays, RNA affinity purification followed by mass spectrometry, and RNA screening within protein libraries [ 88 ]. In addition, a systematic screen using CRISPR/Cas targeting RNA-binding domains of a large series of RBPs can be used to identify interacting RBPs in malignancies as recently described for AML [ 89 ]. So far, these techniques were employed for the analysis of whole cell lysates.…”

Section: Methodical Strategies and Specific Challenges Regarding Mmentioning

confidence: 99%

Expression, Regulation and Function of microRNA as Important Players in the Transition of MDS to Secondary AML and Their Cross Talk to RNA-Binding Proteins

Bauer

Vaxevanis

Heimer

et al. 2020

IJMS

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Myelodysplastic syndromes (MDS), heterogeneous diseases of hematopoietic stem cells, exhibit a significant risk of progression to secondary acute myeloid leukemia (sAML) that are typically accompanied by MDS-related changes and therefore significantly differ to de novo acute myeloid leukemia (AML). Within these disorders, the spectrum of cytogenetic alterations and oncogenic mutations, the extent of a predisposing defective osteohematopoietic niche, and the irregularity of the tumor microenvironment is highly diverse. However, the exact underlying pathophysiological mechanisms resulting in hematopoietic failure in patients with MDS and sAML remain elusive. There is recent evidence that the post-transcriptional control of gene expression mediated by microRNAs (miRNAs), long noncoding RNAs, and/or RNA-binding proteins (RBPs) are key components in the pathogenic events of both diseases. In addition, an interplay between RBPs and miRNAs has been postulated in MDS and sAML. Although a plethora of miRNAs is aberrantly expressed in MDS and sAML, their expression pattern significantly depends on the cell type and on the molecular make-up of the sample, including chromosomal alterations and single nucleotide polymorphisms, which also reflects their role in disease progression and prediction. Decreased expression levels of miRNAs or RBPs preventing the maturation or inhibiting translation of genes involved in pathogenesis of both diseases were found. Therefore, this review will summarize the current knowledge regarding the heterogeneity of expression, function, and clinical relevance of miRNAs, its link to molecular abnormalities in MDS and sAML with specific focus on the interplay with RBPs, and the current treatment options. This information might improve the use of miRNAs and/or RBPs as prognostic markers and therapeutic targets for both malignancies.

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“…A highly diverse spectrum of soluble and cellular factors within the TME of HNSSC have been described to be involved in the immune escape of this disease [ 66 ]. Thus, the TME has the ability to adapt to environmental demand depending on the tumor metabolism and hypoxia.…”

Section: Tumor Microenvironment and Hnsccmentioning

confidence: 99%

Immune Escape Mechanisms and Their Clinical Relevance in Head and Neck Squamous Cell Carcinoma

Seliger

Massa

Yang

et al. 2020

IJMS

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Immunotherapy has been recently approved for the treatment of relapsed and metastatic human papilloma virus (HPV) positive and negative head and neck squamous cell carcinoma (HNSCC). However, the response of patients is limited and the overall survival remains short with a low rate of long-term survivors. There exists growing evidence that complex and partially redundant immune escape mechanisms play an important role for the low efficacy of immunotherapies in this disease. These are caused by diverse complex processes characterized by (i) changes in the expression of immune modulatory molecules in tumor cells, (ii) alterations in the frequency, composition and clonal expansion of immune cell subpopulations in the tumor microenvironment and peripheral blood leading to reduced innate and adaptive immune responses, (iii) impaired homing of immune cells to the tumor site as well as (iv) the presence of immune suppressive soluble and physical factors in the tumor microenvironment. We here summarize the major immune escape strategies of HNSCC lesions, highlight pathways, and molecular targets that help to attenuate HNSCC-induced immune tolerance, affect the selection and success of immunotherapeutic approaches to overcome resistance to immunotherapy by targeting immune escape mechanisms and thus improve the HNSCC patients’ outcome.

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Targeting the Immune Microenvironment in the Treatment of Head and Neck Squamous Cell Carcinoma

Cited by 68 publications

References 147 publications

Hippo Pathway and YAP Signaling Alterations in Squamous Cancer of the Head and Neck

Hippo Pathway and YAP Signaling Alterations in Squamous Cancer of the Head and Neck

Expression, Regulation and Function of microRNA as Important Players in the Transition of MDS to Secondary AML and Their Cross Talk to RNA-Binding Proteins

Immune Escape Mechanisms and Their Clinical Relevance in Head and Neck Squamous Cell Carcinoma

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