Ideal Timing of Immunotherapy With Radiation in Murine Tumor Models

Abstract

218 mm (p Z 0.028). Similarly, anti-PD-1 therapy with RT resulted in significantly longer survival than PD-1 blockade therapy alone (29 days vs 19 days; p Z 0.021). The mean tumor size on day 19 at the primary site was 103 mm (anti-PD-1) and 26.2 mm (anti-PD-1 + RT) (p Z 0.043). Secondary tumor growth was 197.8 mm and 88.4 mm for PD-1 therapy alone or with RT (p Z 0.037). RT alone to the primary tumor had no suppressive effect on the distant tumor growth. Flow analysis confirmed the presence of anti-melanoma PD-1+ CD8+ effector T cells in both primary and distant tumor sites. Conclusions: In our preclinical models, the addition of RT to PD-1 blockade (PD-1 KO and anti-PD-1 antibody) suppressed tumor growth at both radiated and non-radiated sites, and successfully recapitulated the clinical abscopal effect of RT. Two mice developed anti-melanoma immunity and did not exhibit melanoma growth upon rechallenge. These results provide a rationale for testing RT and PD-1 blockade combination therapy in a clinical setting. Author Disclosure: S.S. Park: A. Employee; Mayo Clinic. E. Research Grant; RSNA Research Scholar Grant Recipient. H. Dong: A. Employee; Mayo Clinic. W. Zhao: A. Employee; Mayo Clinic. M.P. Grams: A. Employee; Mayo Clinic. X. Liu: A. Employee; Mayo Clinic. S.M. Harrington: A. Employee; Mayo Clinic. K.M. Furutani: A. Employee; Mayo Clinic. C.J. Krco: A. Employee; Mayo Clinic. K.R. Olivier: A. Employee; Mayo Clinic. S.N. Markovic: A. Employee; Mayo Clinic. E.D. Kwon: A. Employee; Mayo Clinic.