Tumor growth limited to subcutaneous site vs tumor growth in pulmonary site exhibit differential effects on systemic immunities

Abstract

To evaluate systemic immunity associated with tumor growth limited to a subcutaneous site versus growth proceeding at multiple tumor sites, we established syngeneic mouse subcutaneous and pulmonary tumor models by local subcutaneous and intravenous injection of colon carcinoma CT26 cells. We found that splenic myeloid-derived suppressor cell (MDSC) levels were significantly increased in the subcutaneous tumor model but not in the pulmonary tumor model. Furthermore, both CD4+ and CD8+ T cells as well as CD4+ Foxp3+ T cells were significantly decreased in the subcutaneous tumor model and were largely unchanged in the pulmonary tumor model. In addition, the subcutaneous model, but not the pulmonary model, displayed a Th1 polarization bias. This bias was characterized by decreased IL-4, IL-9, and IL-10 production, whereas the pulmonary model displayed increased production of IL-10. These results suggest that the mode of tumor development has differential effects on systemic immunity that may, in turn, influence approaches to treatment of cancer patients.

Dietary Supplementation of Selenoneine-Containing Tuna Dark Muscle Extract Effectively Reduces Pathology of Experimental Colorectal Cancers in Mice

“…MDSCs represent a heterogeneous cell population whose members share a capacity to exert immunological suppressor functions [ 5 , 6 ], and whose numbers increase in the spleen with the growth of human and murine cancers [ 7 , 8 ]. In contrast, both CD4 + and CD8 + T cells, as well as CD4 + Foxp3 + regulatory T cells (Tregs) decrease significantly in the spleen, which leads to a reduction of all representative cytokines such as IFN-γ, IL-4, and IL-10 in allograft colorectal tumor models compared to normal controls [ 9 ].…”

Cytokine Expression and Macrophage Localization in Xenograft and Allograft Tumor Models Stimulated with Lipopolysaccharide

“…These observations correlated with the MHC class II and CD80 expression on CD11b + cells ( Figure 1B, C). In addition, MDSCs were identified by the co-expression of the myeloid lineage differentiation antigens Gr-1 and CD11b of mice [19,20]. The percentages of Gr-1 dim CD11b + and Gr-1 hi CD11b + MDSCs in nude mice were higher than those in WT mice ( Figure 1D).…”

“…The spleen traps pathogens and antigens in circulating blood and initiates innate and adaptive immune responses. Macrophages exist in the spleen in a steady state, whereas MDSCs migrate there during inflammation or cancer progression [16,18]. To determine the differences in the expression and functions of M1 macrophages and MDSC subsets, HT29 and CT26 tumor-bearing mice were administered with LPS as described above, and their splenocytes were stained for M1 macrophages.…”

“…MDSCs represent a heterogeneous cell population whose members share a capacity to exert a suppressor function [8][9][10] and whose numbers increase with the growth of human and murine cancers [11][12][13][14][15][16]. Although MDSCs are characterized by the dual expression of Gr-1 and CD11b in mice and are regarded as a distinct population from M2 macrophages, they share many characteristics in terms of mechanisms that sustain and promote tumor growth [2].…”

Suppression effect on IFN‑γ of adipose tissue‑derived mesenchymal stem cells isolated from β2‑microglobulin‑deficient mice

“…. Spleen cells were isolated as described previously (17). To decide the optimal cell number of spleen cells for MLR to detect IFN-γ production, spleen cells (1x10 5 -16x10 5 ) from recipients (30-week-old male C57BL/6-Ly5.1 mice) were mixed with spleen cells (1x10 5 -16x10 5 ) from allogenic donors (30-week-old male BALB/c mice).…”