The confluence of stereotactic ablative radiotherapy and tumor immunology

Abstract

Stereotactic radiation approaches are gaining more popularity for the treatment of intracranial as well as extracranial tumors in organs such as the liver and lung. Technology, rather than biology, is driving the rapid adoption of stereotactic body radiation therapy (SBRT), also known as stereotactic ablative radiotherapy (SABR), in the clinic due to advances in precise positioning and targeting. Dramatic improvements in tumor control have been demonstrated; however, our knowledge of normal tissue biology response mechanisms to large fraction sizes is lacking. Herein, we will discuss how SABR can induce cellular expression of MHC I, adhesion molecules, costimulatory molecules, heat shock proteins, inflammatory mediators, immunomodulatory cytokines, and death receptors to enhance antitumor immune responses.

Figure 1

Confluence of SABR and Immunotherapy. Apoptosis can be initiated by SABR-induced DNA damage and upregulation of the p53 tumor suppressor gene. In addition, apoptosis can be triggered by SABR-induced damage to the cellular lipid membrane, which can induce ceramide formation and activate the SAPK/JNK signaling pathway. Thus, SAPK/JNK can upregulate PKR expression, which can induce MHC and cytokines via NF-κB. SABR can induce cellular expression of MHC Class I, adhesion molecules, costimulatory molecules, heat shock proteins, inflammatory mediators, immunomodulatory cytokines, and death receptors.