Immune checkpoint inhibitors and radiotherapy—concept and review of current literature

Traditional chemotherapeutic agents non-selectively eliminate cancer cells at the expense of normal tissue; in an attempt to minimize such effects, a new class of targeted agents, immunotherapy, was introduced in the late 1950s with the discovery of interferons and the development of the first cancer vaccine. Ever since, immunotherapy evolved, exploiting different cellular mechanisms including dendritic cell therapy, monoclonal antibodies, and cytokines. Immune checkpoint inhibitors (ICPI) are the most recent subclass of this family and we herein review the basis of exploiting this new subclass of immunotherapy with radiotherapy in the context of studies evaluating their effects on human subjects and focusing on the synergism between the molecular pathways operating in the background. PubMed was searched for studies evaluating the combined use of ICPI and radiotherapy among human subjects. The majority of studies noted an increased response rate in patients receiving combined therapy with no significant increase in toxicity. Outcomes varied among the different ICPI, and treatment with combined anti-PD-1 and anti-CTLA-4 had a higher response rate compared to either modality alone. Synergistic use of ICPI and radiotherapy has the potential to improve survival, however the specifics regarding treatment plan is dependent on a myriad of factors including the genetic and molecular makeup of the tumor as well as the patient.