Radiotherapy and immunotherapy combination in head and neck cancer: Does current failure qualify as an ending or is it a key to future success?

Radiation has been the mainstay of treatment in head and neck squamous cell carcinoma (HNSCC), both in the early stage and locally advanced (LA) settings, depending on the site of origin and the availability of modern surgical approaches. Traditionally, ionizing radiation entrains its cytotoxic activity through induction of irreversible DNA damage, which leads to inability of cellular replication and eventually forces the cell to death via either apoptosis, necrosis, autophagy or mitotic catastrophe [1]. However, over the past two decades, it has been suggested that apart from direct effects on Indeed, radiation is known to foster antitumor immunity and elicit immunogenic cell death (ICD). ICD is a new form of tumor cell death which is directly associated with the release of damage-associated molecular patterns (DAMPs) from radiation-affected dying cells [3]. The production of DAMPs enhances the antigen-presenting procedure resulting in activation of effector T cells [4]. Additional beneficial effects of radiation include Although radiation alone is insufficient to produce efficacious anti-tumor response, its complex effects within the TME can be potentially exploited