Radiotherapy as salvage therapy and an adjunct to immunotherapy: exploring local and abscopal mechanisms to overcome immunotherapy resistance: a narrative review.

Abstract

Background and objective: Immune checkpoint inhibitors (ICIs) have ushered in a new era of therapies and play a significant role in the clinical treatment of a variety of tumors. However, immune resistance has increasingly created a bottleneck in treatment, making the question of how to overcome drug resistance an urgent issue to address. In this article, the mechanism of drug resistance is briefly described with a focus on how radiotherapy (RT) acts on the immune system to reverse immunotherapy failure. Combinations of existing treatment modalities need to be optimized to overcome resistance problems. Research has shown that some RT modalities reverse immune resistance or enhance efficacy when used in combination, which shows some value for immune resistance and is worthy of in-depth research.

Methods: In this review, we searched the literature published from 2000 to 2023 surrounding immunotherapy, RT and cancer.

Key content and findings: Based on the immune effects and immunosuppressive effects induced by RT, this review examined the preclinical rationales of RT and its clinical results. The findings indicate that RT might provide a novel regimen for patients with locally advanced tumors, especially oligometastatic tumors.

Conclusions: Salvage therapy with RT after immunotherapy resistance is the focus of current research. Other strategies, such as multidrug combination therapies, have made preliminary progress in preclinical experiments. Further research on the roles of different RT doses, fractionation regimens, and other treatment sequences in salvage therapy need to be conducted in the future. The optimal site and timing of low-dose radiotherapy are also undetermined, and prospective studies are need to determine the best regimen for optimizing patient treatment.