The Evolving Interplay of SBRT and the Immune System, along with Future Directions in the Field

SIMPLE SUMMARY: We provide this commentary of stereotactic body radiotherapy (SBRT), and describe our evolving understanding of this treatment approach, its effects on the immune system, and the ability to stimulate immune cells to further recognize and attack cancer. The aim of this work is to describe our current knowledge of how SBRT effects the environment within the tumor and the immune cells present, whether timing the combination of this treatment with that of immunotherapy may have an impact on the body’s own immune response, and what the latest approaches in the field are in regards to this radiation treatment modality. Among these latest and exciting developments is Personalized Ultrafractionated Stereotactic Adaptive Radiation Therapy, known as PULSAR. This latest approach is described in detail herein, and may represent a leading novel method for adapting radiation treatments to treatment-induced tumor changes over time and stimulating the body’s immune response against tumor cells. ABSTRACT: In this commentary, we describe the potential of highly ablative doses utilizing Stereotactic Body Radiation Therapy (SBRT) in single or few fractions to enhance immune-responsiveness, how timing of this approach in combination with immune-checkpoint inhibitors may augment treatment-effect, and whether Personalized Ultrafractionated Stereotactic Adaptive Radiation Therapy (PULSAR) is an avenue for future advancement in the continued endeavor to foster a systemic effect of therapy beyond the radiation treatment field. The ablative potential of SBRT may support an increase in tumor-antigen presentation, enhancement of immune-stimulatory components, and an improvement in tumor-microenvironment immune cell infiltration. Furthermore, the latest advancement of ablative radiation delivery is PULSAR-based therapy, whereby ablative doses are delivered in pulses of treatment that may be several weeks apart, combined with adaptive treatment to tumor changes across time. The benefits of this novel approach include the ability to optimize direct tumor control by assessment of tumor size and location via dedicated imaging acquired prior to each delivered pulse, and further potentiation of immune recognition through combination with concurrent immune-checkpoint blockade.