Enhancement of antitumor immunity by low-dose total body irradiationis associated with selectively decreasing the proportion and number of T regulatorycells

Abstract

Low-dose total body irradiation (LTBI) is used in the treatment of somecancers mainly for immune enhancement rather than cell killing. However, themechanism underlying LTBI remains unknown. In this study, by analyzing theimmune patterns of lymphocytes, we found that the percentage and absolutenumber of CD4+CD25+Foxp3+ regulatory T cells are markedly decreased in naive mice following treatmentwith LTBI. On the contrary, the CD4+CD44+/CD8+CD44+ effector-memory T cells are greatly increased. Importantly, naive mice treatedwith dendritic cell-gp100 tumor vaccines under LTBI induced an enhancementof antigen-specific proliferation and cytotoxicity as well as interferon-γ(IFN-γ) secretion against F10 melanoma tumor challenge, compared to treatmentwith either the tumor vaccine or LTBI alone. Consequently, the treatment resultedin a reduced tumor burden and prolonged mouse survival. Our data demonstratethat LTBIs enhancement of antitumor immunity was mainly associatedwith selectively decreasing the proportion and number of T regulatory cells,implying the potential application of the combination of LTBI and a tumorvaccine in antitumor therapy. © 2010 CSI and USTC. All rights reserved.