Enhancement of antitumor immunity by low-dose total body irradiationis associated with selectively decreasing the proportion and number of T regulatory cells.
Low-dose total body irradiation (LTBI) is used in the treatment of some cancers mainly for immune enhancement rather than cell killing. However, the mechanism underlying LTBI remains unknown. In this study, by analyzing the immune patterns of lymphocytes, we found that the percentage and absolute number of CD4(+)CD25(+)Foxp3(+) regulatory T cells are markedly decreased in naive mice following treatment with LTBI. On the contrary, the CD4(+)CD44(+)/CD8(+)CD44(+) effect or-memory T cells are greatly increased. Importantly, naive mice treated with dendritic cell-gp 100 tumor vaccines under LTBI induced an enhancement of antigen-specific proliferation and cytotoxicity as well as interferon-gamma (IFN-gamma) secretion against F10 melanoma tumor challenge, compared to treatment with either the tumor vaccine or LTBI alone. Consequently, the treatment resulted in a reduced tumor burden and prolonged mouse survival. Our data demonstrate that LTBI's enhancement of antitumor immunity was mainly associated with selectively decreasing the proportion and number of T regulatory cells,implying the potential application of the combination of LTBI and a tumor vaccine in antitumor therapy.
Department of Immunology, Shanghai Medical College,Institute for Immunobiology, Key Laboratory of Molecular Medicine of Ministryof Education, Fudan University, Shanghai, China.
Rongjun
R
Liu
Shudao
S
Xiong
Lei
L
Zhang
Yiwei
Y
Chu
D000818:Animals; D019496:Cancer Vaccines / Q000276:immunology / Q000627:therapeutic use; D049109:Cell Proliferation / Q000528:radiation effects*; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology; D005260:Female; D007156:Immunologic Memory / Q000528:radiation effects; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D009368:Neoplasm Transplantation; D009369:Neoplasms / Q000276:immunology* / Q000473:pathology; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology* / Q000528:radiation effects*; D014916:Whole-Body Irradiation
D019496:Cancer Vaccines; D007371:Interferon-gamma