Immune Check-Point Inhibitors and Standard Chemoradiotherapy in Definitive Head and Neck Cancer Treatment

Felice, Francesca De; Musio, Daniela; Tombolini, Vincenzo

doi:10.3390/jpm11050393

Cited by 7 publications

(6 citation statements)

References 29 publications

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“…However, for patients with HNSCC the only targeted therapy approved is cetuximab, a monoclonal antibody against epidermal growth factor receptor (EGFR) (6,9). Recently, pembrolizumab and nivolumab, immunotherapeutic agents, have been approved for HNSCC (10,11). Nonetheless, patients treated with targeted therapy such as cetuximab combined with radiotherapy develop resistance (6,12) and less than 20% of HNSCC patients treated with immunotherapy achieve a lasting response (13).…”

Section: Introductionmentioning

confidence: 99%

Targeted Next-Generation Sequencing of Cancer-Related Genes in a Norwegian Patient Cohort With Head and Neck Squamous Cell Carcinoma Reveals Novel Actionable Mutations and Correlations With Pathological Parameters

et al. 2021

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BackgroundTargeted next-generation sequencing (NGS) is increasingly applied in clinical oncology to advance personalized treatment. Despite success in many other tumour types, use of targeted NGS panels for assisting diagnosis and treatment of head and neck squamous cell carcinomas (HNSCC) is still limited.AimThe focus of this study was to establish a robust NGS panel targeting most frequent cancer mutations in long-term preserved formalin-fixed paraffin-embedded (FFPE) tissue samples of HNSCC from routine diagnostics.Materials and MethodsTumour DNA obtained from archival FFPE tissue blocks of HNSCC patients treated at Haukeland University Hospital between 2003-2016 (n=111) was subjected to mutational analysis using a custom made AmpliSeq Library PLUS panel targeting 31 genes (Illumina). Associations between mutational burden and clinical and pathological parameters were investigated. Mutation and corresponding clinicopathological data from HNSCC were extracted for selected genes from the Cancer Genome Atlas (TCGA) and used for Chi-square and Kaplan-Meier analysis.ResultsThe threshold for sufficient number of reads was attained in 104 (93.7%) cases. Although the specific number of PCR amplified reads detected decreased, the number of NGS-annotated mutations did not significantly change with increased tissue preservation time. In HPV-negative carcinomas, mutations were detected mainly in TP53 (73.3%), FAT1 (26.7%) and FLG (16.7%) whereas in HPV-positive, the common mutations were in FLG (24.3%) FAT1 (17%) and FGFR3 (14.6%) genes. Other less common pathogenic mutations, including well reported SNPs were reproducibly identified. Presence of at least one cancer-specific mutations was found to be positively associated with an extensive desmoplastic stroma (p=0.019), and an aggressive type of invasive front (p=0.035), and negatively associated with the degree of differentiation (p=0.041). Analysis of TCGA data corroborated the association between cancer-specific mutations and tumour differentiation and survival analysis showed that tumours with at least one mutation had shorter disease-free and overall survival (p=0.005).ConclusionsA custom made targeted NGS panel could reliably detect several specific mutations in archival samples of HNSCCs preserved up to 17 years. Using this method novel associations between mutational burden and clinical and pathological parameters were detected and actionable mutations in HPV-positive HNSCC were discovered.

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Section: Introductionmentioning

confidence: 99%

Targeted Next-Generation Sequencing of Cancer-Related Genes in a Norwegian Patient Cohort With Head and Neck Squamous Cell Carcinoma Reveals Novel Actionable Mutations and Correlations With Pathological Parameters

et al. 2021

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“…Immunotherapy is increasingly becoming an important means of cancer treatment, the application of immune checkpoint inhibitors has improved the prognosis of some cancer patients [ 33 , 34 ]. Therefore, we collected the expression data of 60 common immune checkpoints [ 27 ], using Pearson's correlation analyzed the relationship between SERCA3 expression and immune checkpoints.…”

Section: Resultsmentioning

confidence: 99%

Role of SERCA3 in the Prognosis and Immune Function in Pan-Cancer

Li²,

Huang

et al. 2022

Journal of Oncology

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The sarcoendoplasmic reticulum calcium adenosine triphosphatase (ATPase) 3 (SERCA3), a member of the SERCA protein family, is located at the endoplasmic reticulum. Its main function is to pump Ca2+ into the endoplasmic reticulum and is involved in maintaining intracellular calcium homeostasis and signal transduction, which are very important factors impacting cancer development and progression. However, the specific role of SERCA3 in cancer remains unclear. Our study, for the first time, comprehensively analyzed the SERCA3 expression profile in multiple cancers and its prognostic value in different cancers using bioinformatics. Furthermore, TCGA database was applied to evaluate the certain correlation of SERCA3 expression with immune modulator genes, immune checkpoints, immune cell infiltration, TMB, and MSI. The results revealed that in many cancers, SERCA3 expression was markedly decreased, which was related to poor prognosis. Additionally, we noticed that SERCA3 expression was correlated with TNM classification and WHO cancer stages in some cancer types. The Pearson correlation analysis showed that SERCA3 expression was closely associated with chemokines, chemokine receptors, MHC, immune activation genes, and immunosuppressive genes. In most cancer types, SERCA3 expression was also associated with immune checkpoints, including PDCD1 and CTLA-4. Further analysis suggested that SERCA3 was significantly correlated with CD8+ T cells, and regulatory T cells. Additionally, pan-cancer analysis confirmed that SERCA3 expression was related to TMB and MSI. In conclusion, these results offer a new insight into the functions and effects of SERCA3 in pan-cancer, and further provide some basis for considering SERCA3 as a potential cancer treatment target and biomarker.

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“…The first ICI drug approved by the FDA for HNSCC therapy was an anti PD-1 agent Nivolumab, in 2016. Currently, PD-1 drugs nivolumab and pembrolizumab, PD-L1 drugs atezolizumab, durvalumab, avelumab, and CTLA-4 ipilimumab and tremelimumab are tested in the treatment of HNSCC [108,109]. In a study by Estremera SD et al on a preclinical mouse model of HPV+ oral cancer, the therapeutic efficacy of antiPD-1 immunotherapy was enhanced by targeting interferon signaling and CTLA-4 [110].…”

Section: Immune Checkpoint Inhibitors (Icis)mentioning

confidence: 99%

Immunology of Oral Squamous Cell Carcinoma—A Comprehensive Insight with Recent Concepts

Venkatesiah

Augustine

Mishra

et al. 2022

Life

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This review aims to understand the concept of oral cancer immunology through the notion of immune profiling, immunoediting and immunotherapy, and to gain knowledge regarding its application for the management of oral cancer patients. Oral cancer is an immunogenic tumor where the cells of the tumor microenvironment play an important role in tumorigenesis. Understanding the mechanism of these modulations can help design immunotherapeutic strategies in oral cancer patients. This article gives an overview of immunomodulation in the oral cancer tumor microenvironment, with concepts of immune profiling, immunoediting and immunotherapy. English literature searches via Google Scholar, Web of Science, EBSCO, Scopus, and PubMed database were performed with the key words immunology, tumor microenvironment, cells, cross talk, immune profiling, biomarkers, inflammation, gene expression, techniques, immunoediting, immunosurveillance, tumor escape, immunotherapy, immune checkpoint inhibitors, vaccines in cancer, oral cancer, and head and neck cancer. Original research articles, reviews, and case reports published from 2016–2021 (n = 81) were included to appraise different topics, and were discussed under the following subsections. Literature published on oral cancer immunology reveals that oral cancer immune profiling with appropriate markers and techniques and knowledge on immunoediting concepts can help design and play an effective role in immunotherapeutic management of oral cancer patients. An evaluation of oral cancer immunology helps to determine its role in tumorigenesis, and immunotherapy could be the emerging drift in the effective management of oral cancer.

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Immune Check-Point Inhibitors and Standard Chemoradiotherapy in Definitive Head and Neck Cancer Treatment

Cited by 7 publications

References 29 publications

Targeted Next-Generation Sequencing of Cancer-Related Genes in a Norwegian Patient Cohort With Head and Neck Squamous Cell Carcinoma Reveals Novel Actionable Mutations and Correlations With Pathological Parameters

Targeted Next-Generation Sequencing of Cancer-Related Genes in a Norwegian Patient Cohort With Head and Neck Squamous Cell Carcinoma Reveals Novel Actionable Mutations and Correlations With Pathological Parameters

Role of SERCA3 in the Prognosis and Immune Function in Pan-Cancer

Immunology of Oral Squamous Cell Carcinoma—A Comprehensive Insight with Recent Concepts

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