KMT2D Loss Promotes Head and Neck Squamous Carcinoma Through Enhancer Reprogramming and Modulation of Immune Microenvironment

Callahan, S. Carson; Divenko, Margarita; Barrodia, Praveen; Singh, Anand K.; Arslan, Emre; Liu, Zhiyi; Yang, Jiah; Anvar, Nazanin Esmaeili; Amit, Moran; Xie, Tongxin; Jiang, Shan; Schulz, Jonathan; Tang, Ming; Myers, Jeffrey N.; Rai, Kunal

doi:10.1101/2021.09.21.461314

Cited by 3 publications

(1 citation statement)

References 76 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In the TIME, cancer cells escape immune-mediated cell death by utilizing epigenetic mechanisms to escape host immune recognition and immunogenicity [31,32]. In the tumor microenvironment (TME), in addition to cancer cells, immune cells also undergo various epigenetic modifications that alter their effector cytokine expression, cancer immunosurveillance, immune-checkpoint molecule expression, and tumor-associated antigen presentation with MHC molecules [33,34]. Additionally, epigenetic modulators such as DNA methyltransferase inhibitors (DNMTis) and histone deacetylase inhibitors (HDACis) can re-program the TIME to increase the susceptibility of tumor cells to cytotoxic T-cellmediated killing, leading to enhanced anti-tumor immune responses [35,36].…”

Section: Introductionmentioning

confidence: 99%

Epigenetic Perspective of Immunotherapy for Cancers

Keshari

Barrodia

Singh

2023

Cells

Self Cite

View full text Add to dashboard Cite

Immunotherapy has brought new hope for cancer patients in recent times. However, despite the promising success of immunotherapy, there is still a need to address major challenges including heterogeneity in response among patients, the reoccurrence of the disease, and iRAEs (immune-related adverse effects). The first critical step towards solving these issues is understanding the epigenomic events that play a significant role in the regulation of specific biomolecules in the context of the immune population present in the tumor immune microenvironment (TIME) during various treatments and responses. A prominent advantage of this step is that it would enable researchers to harness the reversibility of epigenetic modifications for their druggability. Therefore, we reviewed the crucial studies in which varying epigenomic events were captured with immuno-oncology set-ups. Finally, we discuss the therapeutic possibilities of their utilization for the betterment of immunotherapy in terms of diagnosis, progression, and cure for cancer patients.

show abstract

Section: Introductionmentioning

confidence: 99%

Epigenetic Perspective of Immunotherapy for Cancers

Keshari

Barrodia

Singh

2023

Cells

Self Cite

View full text Add to dashboard Cite

show abstract

Circulating tumour DNA alterations: emerging biomarker in head and neck squamous cell carcinoma

Huang¹,

Duijf²,

Sriram³

et al. 2023

J Biomed Sci

View full text Add to dashboard Cite

Head and Neck cancers (HNC) are a heterogeneous group of upper aero-digestive tract cancer and account for 931,922 new cases and 467,125 deaths worldwide. About 90% of these cancers are of squamous cell origin (HNSCC). HNSCC is associated with excessive tobacco and alcohol consumption and infection with oncogenic viruses. Genotyping tumour tissue to guide clinical decision-making is becoming common practice in modern oncology, but in the management of patients with HNSCC, cytopathology or histopathology of tumour tissue remains the mainstream for diagnosis and treatment planning. Due to tumour heterogeneity and the lack of access to tumour due to its anatomical location, alternative methods to evaluate tumour activities are urgently needed. Liquid biopsy approaches can overcome issues such as tumour heterogeneity, which is associated with the analysis of small tissue biopsy. In addition, liquid biopsy offers repeat biopsy sampling, even for patients with tumours with access limitations. Liquid biopsy refers to biomarkers found in body fluids, traditionally blood, that can be sampled to provide clinically valuable information on both the patient and their underlying malignancy. To date, the majority of liquid biopsy research has focused on blood-based biomarkers, such as circulating tumour DNA (ctDNA), circulating tumour cells (CTCs), and circulating microRNA. In this review, we will focus on ctDNA as a biomarker in HNSCC because of its robustness, its presence in many body fluids, adaptability to existing clinical laboratory-based technology platforms, and ease of collection and transportation. We will discuss mechanisms of ctDNA release into circulation, technological advances in the analysis of ctDNA, ctDNA as a biomarker in HNSCC management, and some of the challenges associated with translating ctDNA into clinical and future perspectives. ctDNA provides a minimally invasive method for HNSCC prognosis and disease surveillance and will pave the way in the future for personalized medicine, thereby significantly improving outcomes and reducing healthcare costs.

show abstract

Mechanisms of Cisplatin Resistance in HPV Negative Head and Neck Squamous Cell Carcinomas

Griso

Acero

Castelo

et al. 2022

Cells

View full text Add to dashboard Cite

Head and neck squamous cell carcinomas (HNSCCs) are the eighth most common cancers worldwide. While promising new therapies are emerging, cisplatin-based chemotherapy remains the gold standard for advanced HNSCCs, although most of the patients relapse due to the development of resistance. This review aims to condense the different mechanisms involved in the development of cisplatin resistance in HNSCCs and highlight future perspectives intended to overcome its related complications. Classical resistance mechanisms include drug import and export, DNA repair and oxidative stress control. Emerging research identified the prevalence of these mechanisms in populations of cancer stem cells (CSC), which are the cells mainly contributing to cisplatin resistance. The use of old and new CSC markers has enabled the identification of the characteristics within HNSCC CSCs predisposing them to treatment resistance, such as cell quiescence, increased self-renewal capacity, low reactive oxygen species levels or the acquisition of epithelial to mesenchymal transcriptional programs. In the present review, we will discuss how cell intrinsic and extrinsic cues alter the phenotype of CSCs and how they influence resistance to cisplatin treatment. In addition, we will assess how the stromal composition and the tumor microenvironment affect drug resistance and the acquisition of CSCs’ characteristics through a complex interplay between extracellular matrix content as well as immune and non-immune cell characteristics. Finally, we will describe how alterations in epigenetic modifiers or other signaling pathways can alter tumor behavior and cell plasticity to induce chemotherapy resistance. The data generated in recent years open up a wide range of promising strategies to optimize cisplatin therapy, with the potential to personalize HNSCC patient treatment strategies.

show abstract

KMT2D Loss Promotes Head and Neck Squamous Carcinoma Through Enhancer Reprogramming and Modulation of Immune Microenvironment

Cited by 3 publications

References 76 publications

Epigenetic Perspective of Immunotherapy for Cancers

Epigenetic Perspective of Immunotherapy for Cancers

Circulating tumour DNA alterations: emerging biomarker in head and neck squamous cell carcinoma

Mechanisms of Cisplatin Resistance in HPV Negative Head and Neck Squamous Cell Carcinomas

Contact Info

Product

Resources

About