Particle Therapy and the Immune System

Immunosurveillance represents one component of a broader and more complex relationship between the immune system and cancer termed “cancer immunoediting”. Immunoediting is composed of three phases termed the “three Es of immunoediting”: elimination, equilibrium, and escape. Ionizing radiation exerts its cytotoxic effects on tumors directly via DNA strand breakage or indirectly by generating free radicals that result in DNA damage. Stimulation of antitumor immunity is a multistep process controlled by several positive and negative signals. In light of the remarkable success of checkpoint inhibitors, there has been a great interest in combining the agents with radiotherapy (RT). Particle therapy (PT) is a form of external beam RT that uses neutral or charged particles. The number of studies investigating the immunogenicity of PT is limited but increasing. Future preclinical and clinical work should be directed to PT and immunotherapy combinations to test the safety and efficacy of the treatments and to maximize patient outcomes.