Proton beam therapy and immunotherapy: an emerging partnership for immune activation in non-small cell lung cancer

Proton beam therapy (PBT) is becoming an increasingly common option for patients undergoing radiation therapy (RT). With the concurrent emergence of immunotherapy as an effective systemic treatment for historically treatment-resistant disease such as advanced non-small cell lung cancer (NSCLC), the combination of RT's immunoadjuvant effects with immunotherapy is gaining widespread attention. However, pre-clinical and clinical studies have shown potential immunosuppressive mechanisms associated with conventional RT that may restrict its immunogenic potential. Protons, as charged particles, exhibit both dosimetric and biological differences in normal and cancer cells that may be able to not only enhance the immunoadjuvant effects of RT, but also reduce immunosuppressive mechanisms. Here, we review the rationale, preclinical and clinical evidence, and ongoing efforts in combining PBT with immunotherapy in cancer treatment with a focus on NSCLC.