The Role of Different Immunocompetent Cell Populations in the Pathogenesis of Head and Neck Cancer—Regulatory Mechanisms of Pro- and Anti-Cancer Activity and Their Impact on Immunotherapy

Cancers, Год журнала: 2023, Номер 15(6), С. 1642 - 1642

Опубликована: Март 7, 2023

Head and neck squamous cell carcinoma (HNSCC) is one of the most aggressive heterogeneous groups human neoplasms. HNSCC characterized by high morbidity, accounting for 3% all cancers, mortality with ~1.5% cancer deaths. It was common worldwide in 2020, according to latest GLOBOCAN data, representing seventh prevalent malignancy. Despite great advances surgical techniques application modern combinations cytotoxic therapies, remains a leading cause death low overall survival rate not exceeding 40-60% patient population. The causes patients are its frequent nodal metastases local neoplastic recurrences, as well relatively response treatment severe drug resistance. Much evidence suggests that tumour microenvironment (TME), infiltrating lymphocytes (TILs) circulating various subpopulations immunocompetent cells, such regulatory T cells (CD4

Язык: Английский

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Use of Oleuropein and Hydroxytyrosol for Cancer Prevention and Treatment: Considerations about How Bioavailability and Metabolism Impact Their Adoption in Clinical Routine

Biomedicines, Год журнала: 2024, Номер 12(3), С. 502 - 502

Опубликована: Фев. 23, 2024

The fact that the Mediterranean diet could represent a source of natural compounds with cancer-preventive and therapeutic activity has been object great interest, especially regard to mechanisms action polyphenols found in olive oil leaves. Secoiridoid oleuropein (OLE) its derivative hydroxytyrosol (3,4-dihydroxyphenylethanol, HT) have demonstrated anti-proliferative properties against variety tumors hematological malignancies both vivo vitro, measurable effects on cellular redox status, metabolism, transcriptional activity. With this review, we aim summarize most up-to-date information potential use OLE HT for cancer treatment, making important considerations about bioavailability, OLE- HT-mediated drug dual as pro- antioxidants, likely hampering their clinical routine. Also, focus details available nutritionally relevant concentrations cell viability, homeostasis, inflammation order evaluate if be considered agents or new chemotherapy drugs whenever only is represented by diet.

Язык: Английский

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Less is more: Exploring neoadjuvant immunotherapy as a de-escalation strategy in head and neck squamous cell carcinoma treatment

Cancer Letters, Год журнала: 2024, Номер 598, С. 217095 - 217095

Опубликована: Июль 2, 2024

Язык: Английский

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Therapeutic Vaccination in Head and Neck Squamous Cell Carcinoma—A Review

Vaccines, Год журнала: 2023, Номер 11(3), С. 634 - 634

Опубликована: Март 13, 2023

Therapeutic vaccination is one of the most effective immunotherapeutic approaches, second only to immune checkpoint inhibitors (ICIs), which have already been approved for clinical use. Head and neck squamous cell carcinomas (HNSCCs) are heterogenous epithelial tumors upper aerodigestive tract, a significant proportion these tend exhibit unfavorable therapeutic responses existing treatment options. Comprehending immunopathology choosing an appropriate maneuver seems be promising avenue solving this problem. The current review provides detailed overview strategies, targets, candidates in HNSCC. classical principle inducing potent, antigen-specific, cell-mediated cytotoxicity targeting specific tumor antigen mechanism vaccination, particularly against human papilloma virus positive subset However, approaches such as countering immunosuppressive microenvironment HNSCC co-stimulatory mechanisms also explored recently, with encouraging results.

Язык: Английский

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Targeted Proteomic Quantitation of NRF2 Signaling and Predictive Biomarkers in HNSCC

Molecular & Cellular Proteomics, Год журнала: 2023, Номер 22(11), С. 100647 - 100647

Опубликована: Сен. 15, 2023

The NFE2L2 (NRF2) oncogene and transcription factor drives a gene expression program that promotes cancer progression, metabolic reprogramming, immune evasion, chemoradiation resistance. Patient stratification by NRF2 activity may guide treatment decisions to improve outcome. Here, we developed mass spectrometry-based targeted proteomics assay based on internal standard-triggered parallel reaction monitoring quantify 69 pathway components targets, as well 21 proteins of broad clinical significance in head neck squamous cell carcinoma (HNSCC). We improved an existing acquisition algorithm, called SureQuant, increase throughput, sensitivity, precision. Testing the optimized platform 27 lung upper aerodigestive models revealed 35 responsive proteins. In formalin-fixed paraffin-embedded HNSCCs, signaling intensity positively correlated with NRF2-activating mutations SOX2 protein expression. Protein markers T-cell infiltration one another human papilloma virus infection status. CDKN2A (p16) oncogenic E7 confirmed presence translationally active virus. This work establishes clinically actionable HNSCC biomarker capable quantifying over 600 peptides from frozen or archived tissues under 90 min.

Язык: Английский

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Recent findings on the impact of ErbB receptors status on prognosis and therapy of head and neck squamous cell carcinoma

Frontiers in Medicine, Год журнала: 2023, Номер 10

Опубликована: Фев. 2, 2023

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer type, has often an aggressive course poorly responsive to current therapeutic approaches, so that 5-year survival rates for patients diagnosed with advanced disease lower than 50%. The Epidermal Growth Factor Receptor (EGFR) emerged as established oncogene in HNSCC. Indeed, although HNSCCs are a heterogeneous group of cancers which differ histological, molecular clinical features, EGFR overexpressed or mutated percentage cases up about 90%. Moreover, aberrant expression other members ErbB receptor family, ErbB2, ErbB3 ErbB4, also been reported variable proportions HNSCCs. Therefore, increased expression/activity one multiple receptors found vast majority While signaling long known play critical role tumor growth, angiogenesis, invasion, metastatization resistance therapy, more recent evidence revealed its impact on features cells' biology, such ability evade antitumor immunity. In this paper we will review findings how activity, including associated non-canonical mechanisms, impacts prognosis therapy

Язык: Английский

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A Review of Immunotherapy for Head and Neck Cancer

Journal of Dental Research, Год журнала: 2024, Номер 103(12), С. 1185 - 1196

Опубликована: Окт. 6, 2024

The introduction of immune checkpoint inhibitors (ICIs) to oncological care has transformed the management various malignancies, including head and neck squamous cell carcinoma (HNSCC), offering improved outcomes. first-line treatment recurrent malignant HNSCC for many years was combined platinum, 5-fluorouracil, cetuximab. Recently, ICI pembrolizumab approved as a treatment, with or without chemotherapy, based on tumor percentage programmed-death ligand 1 (PD-L1). Multiple (HN) cancer trials have subsequently explored immunotherapies in combination surgery, and/or radiation. Immunotherapy regimens may be personalized by biomarker, PD-L1 content, mutational burden, microsatellite instability. However, further clinical are needed refine biomarker-driven protocols standardize pathological methods guide regimen timing, sequencing, deescalation. Gaps remain using immunotherapy reverse oral premalignant lesions, particularly high-risk leukoplakias. A phase II nonrandomized controlled trial, nivolumab, showed 2-y cancer-free survival 73%, although larger needed. Guidelines also role dental evaluation before, during, after immunotherapy, specifically regard immune-related adverse events their impact recurrence. Standardized diagnostic coordination strategies close these gaps ensure continued success HN immunotherapy.

Язык: Английский

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Cutting‐Edge Therapy and Immune Escape Mechanisms in EBV‐Associated Tumors

Medicinal Research Reviews, Год журнала: 2025, Номер unknown

Опубликована: Март 12, 2025

Epstein-Barr virus (EBV), the first identified human tumor virus, significantly influences immune microenvironment of associated cancers. EBV-induced expression viral antigens by cells triggers recognition and elicits a pro-inflammatory response. While mild inflammation may help eliminate malignant cells, intense can accelerate progression. Moreover, EBV establish lifelong latency in hosts, characterized low immunogenicity its proteins noncoding RNAs. This enables to evade detection impair cell function, disrupting homeostasis. Consequently, EBV-associated malignancies pose considerable public health challenge globally, often complicating prognosis cancer patients under conventional treatment. With deeper research into oncogenic expressions mechanisms EBV, novel targeted therapies against are gaining prominence. review discusses recent advancements understanding how helps surveillance induce dysfunction. It also examines clinical potential targeting tumors, providing fresh perspectives on therapeutic strategies for these

Язык: Английский

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Proton Treatment Suppresses Exosome Production in Head and Neck Squamous Cell Carcinoma

Cancers, Год журнала: 2024, Номер 16(5), С. 1008 - 1008

Опубликована: Фев. 29, 2024

Proton therapy (PT) is emerging as an effective and less toxic alternative to conventional X-ray-based photon (XRT) for patients with advanced head neck squamous cell carcinomas (HNSCCs) owing its clustered dose deposition dosimetric characteristics. For optimal efficacy, cancer therapies, including PT, must elicit a robust anti-tumor response by effector cytotoxic immune cells in the tumor microenvironment (TME). While tumor-derived exosomes contribute suppression TME, information on effects of PT responses HNSCC not known. In this study, we generated primary from tumors resected patients, irradiated them 5 Gy or XRT, isolated culture supernatants. exposed produced 75% fewer than XRT- non-irradiated cells. This effect persisted proton-irradiated up five days. Furthermore, observed that were identical morphology immunosuppressive (suppression IFN-γ release peripheral blood mononuclear cells) those photon-irradiated Our results suggest limits suppressive surveillance reducing production can inhibit function.

Язык: Английский

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Knockdown of Ubiquitin-Conjugating Enzyme E2 T Abolishes the Progression of Head and Neck Squamous Cell Carcinoma by Inhibiting NF-Κb Signaling and inducing Ferroptosis

Current Protein and Peptide Science, Год журнала: 2024, Номер 25(7), С. 577 - 585

Опубликована: Апрель 15, 2024

Background: Ubiquitin-conjugating enzyme 2T (UBE2T) has been reported to be associated with uncontrolled cell growth and tumorigenesis in multiple cancer types. However, the understanding of its regulatory role carcinogenesis Head And Neck Squamous Cell Carcinoma (HNSC) is limited. Methods: UBE2T expression HNSC patient samples correlation between patients’ survival rates were evaluated using The Cancer Genome Atlas (TCGA) database. proliferation investigated UM-SCC1 UM-SCC15 cells infected control shUBE2T lentivirus. xenograft mouse model was established examine or without UBE2T. Western blot, qRT-PCR, ferroptosis assays carried out disclose interaction NF-κB signaling ferroptosis. Results: increased noted tumor tissues patients HNSC, correlating a significantly reduced overall time this cohort. Knockdown inhibited growth. Mechanistically, inhibition suppressed induced HNSC. Conclusion: Our study underscores multifaceted illuminating potential as biomarker therapeutic target.

Язык: Английский

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