Tumor microenvironment is not an 'innocent bystander' in the resistance to treatment of head and neck cancers (Review).

Head and neck cancers are still one of the most common types of cancer in the world. They rank in the leading sixth place in terms of incidence globally, and the incidence continues to rise. The mortality rates remain at high levels. Pathological subclassification places squamous cell carcinoma of the head and neck (HNSCC) in the first place concerning the histological forms of head and neck cancers; a tumor with extremely aggressive behavior and high mortality rates. The tumor microenvironment is a very complex ecosystem of cellular and non-cellular components, characterized by unique features, that contribute to the appearance of immunosuppression and diminished anticancer immunity, impacting patient prognosis and treatment outcome. Despite many important advances in therapy, resistance to therapy represents a difficult challenge in HNSCC patients. Tumor progression, metastasis, and response to therapy are all influenced by the complex ecosystem represented by the tumor microenvironment and by the interactions between cellular and non-cellular components of this system. Therefore, the tumor microenvironment, in the light of recent data, is not an innocent bystander. In the last few years, there has been a sustained effort to characterize the tumor microenvironment, to identify targets of response and identify other mechanisms of tumor-specific immune responses, or to discover other biomarkers of response. There is an urgent need to understand how to properly select patients, the therapy sequence, and how to use feasible biomarkers that can help to identify the patient who may obtain the most benefit from available therapies.