Radiotherapy is an important treatment method for malignant tumors. Radiation resistance is the main obstacle to the therapeutic effect of radiotherapy. Cellular metabolic reprogramming is one of the main features of cancer, and it may have an important effect on the therapeutic effect of radiotherapy. Glutamine is closely related to tumor cell biosynthesis and growth. It affects radiotherapy sensitivity by producing antioxidants through decomposition. In addition, the expression patterns and functions of two isoenzymes of glutamine, namely, glutaminase (GLS) and glutaminase 2 (GLS2), are different and have an important influence on the sensitivity of radiotherapy. The utilization of glutamine metabolism in the tumor microenvironment has great research value to improve the efficacy of radiotherapy. This review describes the metabolic characteristics of glutamine in malignant tumors and the sensitization effect of glutamine inhibitors on the efficacy of radiotherapy.

The mechanisms of radiotherapy (RT) in cancer treatment are both by immunity and non-immunity pathways. According to different absorbed doses, the immune modulating effect of RT comprises of tumor microenvironment modulating effect, immune-modulatory effect as well as immune-ablative effect. RT could improve the therapeutic efficacy of immunotherapy, while immunotherapy could enlarge the immunity activating effect induced by RT in turn. Therefore, RT is emerging as a valuable partner of cancer immunotherapy. RT regimens have a vital impact on immunity within tumor microenvironment. Stereotactic body RT (SBRT) has obvious advantages regarding interferon production and abscopal effect. At present, potentially sub-ablative RT regimen of 8 Gy plus 3 fractionations is the most widely used SBRT. Several novel RT regimens, such as hybrid fractionation, singular site irradiation and multisite irradiation, have been designed to maximize the immune induction effect and improve the combination efficacy with immunotherapy in metastatic malignancies. In this review, the latest advances in the immune effect of RT were discussed and novel SBRT regimens were proposed, aiming to provide reference for enhancing the efficacy of radio-immunotherapy or immuno-radiotherapy in clinical practice.