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

Abstract

T cell-deficient mice such as nude mice are often used to generate tumor xenograft for the development of anticancer agents. However, the functionality of the other immune cells including macrophages, dendritic cells (DCs), and myeloid-derived suppressor cells (MDSCs) in the xenograft are largely unknown. Macrophages and dendritic cells (DCs) acquire functionally distinct properties in response to various environmental stimuli; the interaction of these cells with MDSCs in tumor microenvironments regulates cancer progression. Nude mice are less likely to reject human cancer cells because of major histocompatibility complex (MHC) mismatches. The tumor microenvironment in a xenograft, comprising human and mouse cells, exhibits more complex bidirectional signaling and function than that of allograft. Here, we evaluated the differences of myeloid cells between them. Plasma interferon-γ and interleukin-18 concentrations in the xenograft tumor model after lipopolysaccharide (LPS) administration were significantly higher than those in the allograft tumor model. MHC class I, II, and CD80 expression levels were increased in CD11b+ and MDSC populations after LPS administration in the spleen of a xenograft tumor model but not in that of an allograft tumor model. Additionally, the number of CD80- and mannose receptor C type 1 (MRC1)-expressing cells was decreased upon LPS administration in the tumor of the xenograft tumor. These results suggest that functions of macrophages and DCs are sustained in the xenograft, whereas their functions in response to LPS were suppressed in the allograft. The findings will encourage the consideration of the effects of myeloid cells in the xenograft for drug development.

The Effect of a Fast-Releasing Hydrogen Sulfide Donor on Vascularization of Subcutaneous Scaffolds in Immunocompetent and Immunocompromised Mice

“…The high H 2 S treatment even further increased the intensity of the monocyte and macrophage staining with a fold change of 4.2 ± 0.5. In addition, the literature states that nude mice have an exaggerated macrophage response [16]. In accordance with the literature, we observed a higher number of MOMA-2 positive pixels per mm 2 of scaffold, 223,358 ± 71,364 and 72,532 ± 31,919, in the nude mice of the control groups compared to the C57BL/6 mice, respectively ( Figure S1B).…”

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

“…Given the protective effect of STDME against CAC, we next examined the accumulation of MDSCs in the spleen. MDSCs were identified as two populations by the co-expression of the myeloid lineage differentiation antigens Gr-1 and CD11b [ 9 , 30 , 32 ]. The percentages of Gr-1 dim CD11b + and Gr-1 hi CD11b + MDSCs in STDME-fed mice were significantly lower than those in the control group ( Figure 3 ).…”

“…Since MDSCs are myeloid precursors that expand during chronic inflammation and tumor growth, the accumulation of splenic MDSCs is observed in cancer model ( Figure 3 ). MDSCs inhibit both adaptive and innate immunity through a variety of diverse mechanisms [ 9 , 30 , 37 ]. MDSCs that accumulate during tumor growth increase ROS production [ 38 ] and increased ROS suppresses antigen-specific activation of T cells [ 37 , 39 ] and differentiation of MDSCs into mature myeloid cells such as tumoricidal M1-like macrophages [ 37 , 40 ].…”

“…Splenocytes were isolated and cultured as previously described [ 9 , 30 ]. Briefly, splenocytes (4 × 105 cells/well) were cultured for 48 h on flat-bottomed 96 well plates (Corning Costar, Cambridge, MA, USA) coated with 5 μg/mL anti-CD3ε monoclonal antibody (mAb) in 200 μL Roswell Park Memorial Institute (RPMI) 1640 medium (Sigma-Aldrich, St. Louis, MO, USA) containing 50 μM 2-mercaptoethanol (Nacalai Tesque, Inc., Kyoto, Japan) and supplemented with 10% ( v / v ) heat-inactivated fetal bovine serum (FBS) (SAFC Biosciences, Lenexa, KS, USA) and 1% ( v / v ) antibiotic-antimycotic solution (10,000 U/mL penicillin, 10,000 μg/mL streptomycin and 25 μg/mL amphotericin B; Life Technologies, Gaithersburg, MD, USA).…”

M1 Macrophages Promote TRAIL Expression in Adipose Tissue-Derived Stem Cells, Which Suppresses Colitis-Associated Colon Cancer by Increasing Apoptosis of CD133+ Cancer Stem Cells and Decreasing M2 Macrophage Population

“…However, according to our previous results, the tumor-suppressive effect of ASCs cultured at a high density in the xenograft tumor model using athymic nude mice was not significant [25]. Moreover, although it has been reported that the function of macrophages and DCs is maintained in xenograft tumor models using athymic nude mice [55], it remains controversial whether the distribution and function of macrophages and DCs in the tumor microenvironment is normal. However, the current study demonstrated that in the colitis-associated cancer model, ASCs modulated the macrophage population during colon cancer development.…”