Awakening the immune system with radiation: Optimal dose and fractionation

Saumil J Gandhi; Andy J Minn; Robert H Vonderheide; E John Wherry; Stephen M Hahn; Amit Maity

doi:10.1016/j.canlet.2015.03.024

Awakening the immune system with radiation: Optimal dose and fractionation

Cancer Lett. 2015 Nov 28;368(2):185-90. doi: 10.1016/j.canlet.2015.03.024. Epub 2015 Mar 20.

Authors

Saumil J Gandhi¹, Andy J Minn², Robert H Vonderheide³, E John Wherry⁴, Stephen M Hahn⁵, Amit Maity⁶

Affiliations

¹ Department of Radiation Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
² Department of Radiation Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Abramson Family Cancer Research Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
³ Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Abramson Family Cancer Research Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
⁴ Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
⁵ Department of Radiation Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
⁶ Department of Radiation Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. Electronic address: [email protected].

PMID: 25799953
DOI: 10.1016/j.canlet.2015.03.024

Abstract

The importance of ionizing radiation has historically been limited to achieving local control of tumor cells. However, emerging evidence over the last decade suggests an increasingly important role for radiation in amplifying the antitumor immune response elicited by immunomodulatory agents. Combination of radiation with immunotherapy has been shown to elicit powerful systemic responses in several pre-clinical tumor models. Additionally, recent clinical observations support the use of radiation therapy for augmenting antitumor immunity in the metastatic setting. However, radiation dose and fractionation schedules for optimal synergy between radiotherapy and immunotherapy are not well defined. Here we review pre-clinical and clinical data relating to radiation dose and fractionation in the setting of immunotherapy and discuss optimal strategies for combining the two therapies.

Keywords: Dose; Fractionation; Immunotherapy; Radiation.

Publication types

Review

MeSH terms

Animals
Dose Fractionation, Radiation
Dose-Response Relationship, Radiation
Humans
Immune System / radiation effects*
Neoplasms / immunology*
Neoplasms / radiotherapy*
Radiotherapy / methods