title: Irradiation enhances human T-cell function by upregulating CD70 expression on antigen-presenting cells in vitro.
abstract: In addition to the direct killing of tumor cells, radiation therapy can alter the balance of immune cells in vivo due to the differential radiosensitivity of different cell types. The addition of adjuvant radiation therapy before adoptive cell transfer therapy has been shown to enhance antitumor responses in both mouse models and clinical trials. This study examines the effects of in vitro irradiation on the phenotype and function of human antigen-presenting cells. The results indicated that irradiation upregulated CD70 expression on both B cells and mature dendritic cells (DCs). Expression of CD70 on mature DCs was enhanced in a dose-dependent manner, whereas under the same conditions, no significant upregulation of CD80, CD86, or CD40 was observed. The levels of expression of CD70 induced on mature DC by irradiation correlated highly with the ability of those cells to stimulate T-cell proliferation and interferon-γ production. Furthermore, significant reductions in T-cell proliferation and interferon-γ production were seen when CD70 expression on DCs was partially reduced using shRNA, as well as when DCs were incubated with a blocking anti-CD70 antibody. Radiation therapy may therefore enhance T-cell activation in vivo through the CD27 pathway by virtue of its ability to upregulate the expression of CD70 on antigen-presenting cells.
authors.affiliation: Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. jianping_huang@-nih.gov
authors.forename: Jianping
authors.initials: J
authors.lastname: Huang
authors.forename: Qiong J
authors.initials: QJ
authors.lastname: Wang
authors.forename: Shicheng
authors.initials: S
authors.lastname: Yang
authors.forename: Yong F
authors.initials: YF
authors.lastname: Li
authors.forename: Mona
authors.initials: M
authors.lastname: El-Gamil
authors.forename: Steven A
authors.initials: SA
authors.lastname: Rosenberg
authors.forename: Paul F
authors.initials: PF
authors.lastname: Robbins
mesh_terms: D000938:Antigen-Presenting Cells / Q000276:immunology / Q000528:radiation effects*; D053282:CD27 Ligand / Q000276:immunology*; D049109:Cell Proliferation; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology / Q000528:radiation effects; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D018664:Interleukin-12 / Q000378:metabolism; D053759:Interleukin-23 / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000528:radiation effects; D008213:Lymphocyte Activation / Q000276:immunology; D011839:Radiation, Ionizing; D013601:T-Lymphocytes / Q000276:immunology / Q000528:radiation effects*; D015854:Up-Regulation
chemical_list: D053282:CD27 Ligand; D053759:Interleukin-23; D018664:Interleukin-12; D007371:Interferon-gamma