Biological consequences of cancer radiotherapy in the context of oral squamous cell carcinoma

Approximately 50% of subjects with cancer have been treated with ionizing radiation (IR) either as a curative, adjuvant, neoadjuvant or as a palliative agent, at some point during the clinical course of their disease. IR kills cancer cells directly by injuring their DNA, and indirectly by inducing immunogenic cell killing mediated by cytotoxic T cells; but it can also induce harmful biological responses to non-irradiated neighbouring cells (bystander effect) and to more distant cells (abscopal effect) outside the primary tumour field of irradiation. Although IR can upregulate anti-tumour immune reactions, it can also promote an immunosuppressive tumour microenvironment. Consequently, radiotherapy by itself is seldom sufficient to generate an effective long lasting immune response that is capable to control growth of metastasis, recurrence of primary tumours and development of second primary cancers. Therefore, combining radiotherapy with the use of immunoadjuvants such as immune checkpoint inhibitors, can potentiate IR-mediated anti-tumour immune reactions, bringing about a synergic immunogenic cell killing effect. The purpose of this narrative review is to discuss some aspects of IR-induced biological responses, including factors that contributes to tumour radiosensitivity/radioresistance, immunogenic cell killing, and the abscopal effect.