Radiotherapy and blockade of immune checkpoints in treatment of cancer patients

Abstract

Background. Immunotherapy, which aims to use immune defense mechanisms to fight cancer, is a new area of anticancer treatment. A major breakthrough in tumor immunotherapy was the discovery of immune checkpoint proteins, which act as powerful suppressors of the immune system. Humanized monoclonal antibodies, which target these proteins, have proven to be clinically effective in patients with different types of cancer. However, the majority of patients do not respond to checkpoint inhibitor therapy, which necessitates the use of combination strategies to overcome resistance to immunotherapy. In recent years, the combination of radiotherapy and immune checkpoint inhibitors has attracted considerable attention and has been widely studied in preclinical and clinical trials. Much attention is given to the optimization of combined treatment regimens. However, the optimal radiation dose, fractionation scheme, radiation volumes, and radiation sequence in checkpoint inhibitor treatment still remain unclear. Purpose – to analyze and summarize data from preclinical and clinical trials aimed at solving problems related to the choice of optimal doses, fractionation, radiation volume, and sequencing of checkpoint inhibitor immunotherapy and radiotherapy. Materials and methods. For data search, we used Cochrane library and databases (Pubmed, Scopus, Google Scholar). The results of the studies published over the period from 2008 to 2023 were analyzed. Results and discussion. The evidence of the rationality of combining radiotherapy and checkpoint inhibitors in the treatment of cancer patients is shown. The data on the effects of radiation dose and fractionation on antitumor immune responses were analyzed. The results of works that deal with the search for the optimal sequence of radiotherapy and immune checkpoint inhibitors and the selection of the irradiation volume necessary for the generation of an effective systemic antitumor immune response are considered. Conclusions. Combined treatment with radiation therapy and immune checkpoint inhibitors is a promising strategy for patients with metastatic tumors. Preclinical and clinical data indicate that different radiation regimens can cause different effects on antitumor immunity. Further studies of doses and fractionation regimens of radiation therapy, irradiation volume, and the optimal time for each component of combination therapy are needed to determine the conditions for maximizing the immune response. The obtained results will help optimize the combination treatment regimens and wider implementation of such treatment in clinical practice.