Incidence of spontaneous lymphomas in non-experimental NOD/Shi-scid, IL-2Rγnull (NOG) mice.

Severely immunodeficient NOD/Shi-scid, IL-2Rγnull (NOG) mice provide an in vivo model for human cell/tissue transplantation studies. NOG mice were established by combining interleukin-2 receptor-γ chain knockout mice and NOD/Shi-scid mice. They exhibit a high incidence of thymic lymphomas and immunoglobulin (Ig) leakiness. In this study, we assessed the incidence of malignant lymphomas and the occurrence of leakiness in 2,184 non-experimental NOG retired breeder mice aged 16-40 weeks. We established that the total incidence of lymphomas was only 0.60% (13/2,184). Most lymphomas (10/13) occurred in female mice by the age of around 25 weeks. No mice developed Ig leakiness. All lymphomas were derived from the thymus, and consisted mainly of CD3-positive and CD45R-negative lymphoblastic-like cells. Therefore, based on the absence of Ig leakiness and a very low incidence of lymphomas, including thymic lymphomas, NOG mice may be useful in regeneration medicine for xenotransplantation of human embryonic stem (ES) cells or induced pluripotent stem (iPS) cells, and in transplantation experiments involving tumor cells.

Early Tumor-Infiltrating Dendritic Cells Change their Characteristics Drastically in Association with Murine Melanoma Progression.

Dendritic cells (DCs) have a critical effect on the outcome of adaptive immune responses against growing tumors. Tumor-infiltrating dendritic cells (TIDCs) play diverse roles in the regulation of tumor regression or growth, but the characteristics that distinguish those effects are obscure. In this study, we investigated the frequency, phenotype, and function of TIDCs over time from early stages of melanoma growth in mice. Flow cytometric analysis revealed that the tumors were infiltrated by a significant population of CD11c(+) major histocompatibility complex II(+) DCs, especially at an early stage of tumor growth. The allogeneic stimulatory capacity of TIDCs increased with tumor growth, whereas this capacity of DCs in lymph nodes decreased. TIDCs harvested at an early stage of melanoma (early TIDCs) accelerated tumor growth, but those harvested at a late stage (late TIDCs) delayed tumor progression when they were coinjected with melanoma cells. Furthermore, coinjection of early TIDCs failed to induce full immunocompetent maturation of CD8(+) T cells, with much lower expression of IFN-γ, granzyme B, and perforin within the tumor microenvironment. In conclusion, TIDCs change their characteristics from an immunoinhibitory to an immunostimulatory phenotype over time in association with tumor progression.