Emerging Mechanisms and Therapeutic Strategies in Head and Neck Cancer

A special issue of Cells (ISSN 2073-4409).

Deadline for manuscript submissions: 1 March 2026 | Viewed by 317

Special Issue Editors


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Guest Editor
Department of Oro-Maxillo-Facial Surgery and Implantology, Iuliu Hatieganu University of Medicine and Pharmacy, 400000 Cluj-Napoca, Romania
Interests: head and neck oncology; tumor microenvironment; tumor–stroma interaction; treatment resistance; radiotherapy sensitization; targeted therapy; precision oncology

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Guest Editor
1. Department of Haematology, Iuliu Hatieganu University of Medicine and Pharmacy, 400000 Cluj-Napoca, Romania
2. "Ion Chiricuță" Institute of Oncology, Cluj-Napoca, Romania
Interests: translational oncology; hematologic malignancies; stem cell biology; cancer stem cells; immunotherapy; cell-based therapies; tumor microenvironment; precision medicine
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Special Issue Information

Dear Colleagues,

Head and neck cancer (HNC) includes varied tumors arising from the mucosal surfaces of the oral cavity, pharynx, and larynx, characterized by distinct molecular profiles and complex pathogenic pathways. Clinically, these malignancies are associated with significant morbidity and mortality, often requiring multimodal treatment approaches. While treatment advances have improved care, patients with advanced-stage disease or early-stage tumors demonstrating high-risk pathological features remain at elevated risk of poor outcomes due to persistent issues such as therapy resistance, locoregional relapse, and distant dissemination. A deeper understanding of the underlying cellular and molecular mechanisms that drive tumor progression, treatment response, and immune evasion is essential to improve patient outcomes and guide the development of more effective, personalized treatment strategies.

In recent years, significant progress has been made in elucidating the biological complexity of HNC, including the contributions of cancer stem cells, epithelial–mesenchymal transition, tumor–stroma interactions, immune modulation, and the oncogenic impact of viruses such as HPV. These findings are reshaping current perspectives on disease pathogenesis and revealing new opportunities for therapeutic innovation.

For this Special Issue, we invite original research articles and reviews that address emerging mechanisms and therapeutic strategies related to head and neck cancer. Areas of focus may include cellular signaling networks, resistance to conventional and targeted therapies, immunotherapeutic approaches, tumor microenvironment dynamics, biomarker development, and novel treatment combinations. We are particularly interested in studies that bridge basic science with translational and clinical relevance, contributing to advancing precision oncology in HNC.

Dr. Madalina Anca Moldovan
Dr. Ciprian Tomuleasa
Guest Editors

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Keywords

  • tumor microenvironment
  • epithelial–mesenchymal transition (EMT)
  • tumor–stroma interaction
  • treatment resistance
  • radiotherapy sensitization
  • targeted therapy
  • precision oncology

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Published Papers (1 paper)

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Review

19 pages, 783 KB  
Review
Cancer-Associated Fibroblasts-Derived Exosomes as Mediators of Immunotherapy Resistance in Head and Neck Squamous Cell Carcinoma
by Julia Federspiel, Jozsef Dudas, Benedikt Gabriel Hofauer, Barbara Wollenberg and Teresa Bernadette Steinbichler
Cells 2025, 14(24), 1978; https://doi.org/10.3390/cells14241978 - 12 Dec 2025
Abstract
The tumor microenvironment (TME) orchestrates tumor growth, immune evasion, and therapeutic response in head and neck squamous cell carcinoma (HNSCC). Current immune checkpoint inhibitors (ICIs) target the programmed death receptor-1/programmed death-ligand 1 (PD-1/PD-L1) axis and improve survival in recurrent, metastatic, and locally advanced [...] Read more.
The tumor microenvironment (TME) orchestrates tumor growth, immune evasion, and therapeutic response in head and neck squamous cell carcinoma (HNSCC). Current immune checkpoint inhibitors (ICIs) target the programmed death receptor-1/programmed death-ligand 1 (PD-1/PD-L1) axis and improve survival in recurrent, metastatic, and locally advanced HNSCC. Tumor cells produced exosomes directly suppress cytotoxic T-lymphocytes activity by modulating immune checkpoint pathways and disrupting T-cell receptor signaling. Cancer-associated fibroblast-derived exosomes (CAF-Exos) function indirectly by conditioning immune escape and tumor growth. Together, these exosomal populations cooperate to create an immunosuppressive niche that hinders the efficacy of immunotherapies. CAF-Exos induce TME changes that exclude CD8+ T-cells, promote regulatory T-cells (Tregs), and upregulate PD-L1 expression in tumor cells. The bidirectional transfer of microRNAs (miRNAs) between tumor cells and CAFs enhances epithelial–mesenchymal transition (EMT), suppresses cytotoxic lymphocytes, and undermines ICI efficacy. This review article summarizes recent publications about plasma-derived exosomes from HNSCC patients. These exosomes carry tumor and immune checkpoint markers, reflect tumor burden and treatment response, and strongly modulate immune cells by suppressing T- and B-cell activity and promoting immunosuppressive macrophages. We encourage functional and biomechanistic future studies in the field of HNSCC that examine how CAF subtypes exosomes achieve an immunoresistant TME. Full article
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