title: Effects of tumor irradiation on host T-regulatory cells and systemic immunity in the context of adoptive T-cell therapy in mice.
abstract: In this study, we used a murine D5 melanoma model to study the effects of local tumor irradiation on the therapeutic efficacy of adoptive T-cell therapy. Tumor irradiation was delivered in 5 daily fractions (8.5 Gy) to subcutaneous tumors on days 7-11 after tumor inoculation. After the last radiation dose, activated tumor-draining lymph node cells were transferred intravenously followed by intraperitoneal IL-2 administration. Tumor irradiation alone had no significant effect on tumor growth; however, it synergistically enhanced the therapeutic efficacy of T-cell therapy. For 2 days after tumor irradiation there was a significant reduction in T cells, B cells, and CD11c(+) dendritic cells in both the tumor microenvironment and the systemic lymphoid compartments. By days 4-6 after irradiation, the relative reduction in the number of Treg cells within the tumor and the systemic compartments was greater than the reduction in conventional T cells. Furthermore, the suppressive function of the Tregs was significantly impaired in irradiated versus untreated mice. Using effector T cells derived from congenic mice, we found that local tumor irradiation resulted in increased proliferation of donor T cells within the tumor and the systemic lymphoid compartments. Radiation was associated with increased expression of the effector cytokines IFN-γ and TNF-α by donor and host CD4(+) and CD8(+) T cells. Altogether, our data indicate that local tumor irradiation has a distinct modulatory effect on Tregs and can enhance systemic antitumor immunity associated with adoptive T-cell therapy.
authors: Department of Surgery, University of Michigan Comprehensive Cancer Center, Ann Arbor, MI 48109-5932, USA.
authors: Shuang
authors: S
authors: Wei
authors: Martin U
authors: MU
authors: Egenti
authors: Seagal
authors: S
authors: Teitz-Tennenbaum
authors: Weiping
authors: W
authors: Zou
authors: Alfred E
authors: AE
authors: Chang
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000528:radiation effects; D039521:CD11c Antigen / Q000378:metabolism; D049109:Cell Proliferation / Q000528:radiation effects; D003713:Dendritic Cells / Q000528:radiation effects; D016219:Immunotherapy, Adoptive; D007371:Interferon-gamma / Q000096:biosynthesis; D007376:Interleukin-2 / Q000008:administration & dosage / Q000627:therapeutic use; D008198:Lymph Nodes / Q000276:immunology / Q000637:transplantation*; D008545:Melanoma / Q000276:immunology* / Q000532:radiotherapy*; D051379:Mice; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism / Q000528:radiation effects*; D059016:Tumor Microenvironment / Q000528:radiation effects; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D039521:CD11c Antigen; D007376:Interleukin-2; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma
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