biostudies-literatureVyhnankova SMinistry of Health of the Czech Republic - AZV CREuropean Union - Next Generation EUCharles University project COOPERATIO-Onco8844https://www.ebi.ac.uk/biostudies/studies/S-EPMC12469655biostudies-literatureUnknown26(18)Head and neck squamous cell carcinomas (HNSCCs) represent a diverse group of malignancies, both clinically and biologically, with human papillomavirus (HPV) infection playing a significant role. HPV-positive tumours generally tend to have a better prognosis and are driven by oncoproteins E6 and E7. In contrast, HPV-negative tumours typically have a worse prognosis and are often linked to mutations in tumour suppressor genes. HNSCCs exist within a complex environment known as the tumour microenvironment (TME). The TME includes tumour cells, cancer stem cells (CSCs), cancer-associated fibroblasts (CAFs), immune cells, extracellular matrix (ECM), blood vessels, and various signalling molecules. These components support tumour progression, invasion, metastasis, and resistance to treatment. Intercellular signalling within the TME-mediated by cytokines such as IL-6, TGF-b, and galectins-further promotes tumour growth and systemic effects like cachexia. Notably, the TME shares features with granulation tissue during wound healing, supporting the concept of cancer as a chronic, non-resolving wound. Effective therapy must target not only tumour cells but also the dynamic TME.International journal of molecular sciencesCold, Hot, and Lethal-The Tumour Microenvironment and the Immunology of Head and Neck Squamous Cell Carcinoma.PMC12469655NW24-03-00459COOPERATIO-OncoProgramme EXCELES, ID Project No. LX22NPO5102Plzak JVyhnankova SSindelka RSmetana KNetusil JLacina LKolar MChovanec MfalseCold, Hot, and Lethal-The Tumour Microenvironment and the Immunology of Head and Neck Squamous Cell Carcinoma.Head and neck squamous cell carcinomas (HNSCCs) represent a diverse group of malignancies, both clinically and biologically, with human papillomavirus (HPV) infection playing a significant role. HPV-positive tumours generally tend to have a better prognosis and are driven by oncoproteins E6 and E7. In contrast, HPV-negative tumours typically have a worse prognosis and are often linked to mutations in tumour suppressor genes. HNSCCs exist within a complex environment known as the tumour microenvironment (TME). The TME includes tumour cells, cancer stem cells (CSCs), cancer-associated fibroblasts (CAFs), immune cells, extracellular matrix (ECM), blood vessels, and various signalling molecules. These components support tumour progression, invasion, metastasis, and resistance to treatment. Intercellular signalling within the TME-mediated by cytokines such as IL-6, TGF-b, and galectins-further promotes tumour growth and systemic effects like cachexia. Notably, the TME shares features with granulation tissue during wound healing, supporting the concept of cancer as a chronic, non-resolving wound. Effective therapy must target not only tumour cells but also the dynamic TME.2025-01-01T00:00:00Z2025 Sep2026-05-01T03:22:34.702Z2026-05-01T03:11:20.518ZS-EPMC124696554100941310.3390/ijms26188844