neoplasm
• mice show slower progression of inoculated MC38 colon adenocarcinoma tumor cells than wild-type controls
• tumor growth is inhibited during subsequent MC38-mOVA challenge
• mice transplanted with B16F10 melanoma tumor cells show decreased tumor progression
• adoptive transfer of MC38-primed B cells from mutant mice into B cell-deficient mice confers improved protection from tumor progression following MC38 tumor inoculation
• OVA-specific class-switched IgG2c+ B cells from mutant mice transferred into B cell-deficient mice exhibit stronger antitumor effects
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• tumor growth of mice inoculated with MC38 colon adenocarcinoma tumor cells or transplanted with B16F10 melanoma tumor cells is reduced
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• mice treated with azoxymethane/dextran sodium sulfate (AOM/DSS) to induce colitis-associated carcinoma, show reduced weight loss, decreased disease activity index, alleviated phenotypes of tumor-associated inflammation, reduced tumor burden, and ameliorated histopathological changes
• mice with AOM/DSS-induced colitis-associated carcinoma show larger tertiary lymphoid structure formation within colon tumors
• tumors from mice with AOM/DSS-induced CAC show increased transcriptional levels of chemokines CXCR5, CXCL12, CXCL13, CCL19, CCL21
• however, no significant difference is seen in the major histocompatibility complex (MHC) and costimulatory molecules CD86 on the cell surface of B cells in the tumor microenvironment, indicating no effect on priming function of B cells to activate T cells
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immune system
• mice treated with azoxymethane/dextran sodium sulfate (AOM/DSS) to induce colitis-associated carcinoma, show reduced weight loss and decreased disease activity index
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• a higher percentage of class-switched IgG2c+ plasma cells are seen in the mesenteric lymph nodes, the colonic lamina propria of AOM/DSS-induced mice and the tumor-draining lymph nodes of MC38 tumor-bearing mice, indicating enhanced plasma cell differentiation in the tumor microenvironment
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• dendritic cells (DCs,) especially CD103+ type I conventional DCs (key antigen-presenting cells that transport antigens to lymphoid structures and prime tumor-specific CD8+ T cells), are elevated in the TME of the MC38 tumor model mice
• however, no differences in tumor-infiltrating macrophages and NK cells are seen in the MC38 tumor model mice
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• in an ovalbumin (OVA) antigen-based immunization model, mice show a higher percentage of OVA-specific IgG2c+ germinal center B cells in the spleen in the tumor microenvironment
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• in an ovalbumin (OVA) antigen-based immunization model, mice show an increase in OVA-specific IgG2c+ memory B cells in the spleen and bone marrow, indicating promotion of class-switched memory B cells in the tumor microenvironment
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• AOM/DSS-induced mice with colorectal cancer exhibit increased infiltration of CD8+ T cells in colon tumor specimens with no differences in CD4+ T cells, NK cells, and macrophages
• infiltration of CD8+ T Cells and IFN-gamma+ CD8+ T cells in the lamina propria and mesenteric lymph nodes is slightly increased in colon tumor specimens of mice with AOM/DSS-induced colorectal cancer
• MC38 tumor-bearing mice show increased amounts of CD8+ T cells within subcutaneous tumor tissues, and especially increased CD44hiCD62LloCD8+ effector T cells, with elevated levels of cytolytic IFN-gamma and granzyme B production, suggesting that tumor-infiltrating CD8+ T cells may help to limit tumor progression
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• MC38 tumor-bearing mice show increased CD44hiCD62LloCD8+ effector T cells
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• in the MC38 transplantation model, mice show elevated amounts of MC38 cell-specific IgG2c antibodies compared to wild-type mice
• B cells from the tumor-draining lymph nodes secrete higher amounts of IgG2c upon restimulation with irradiated MC38 cells than B cells from wild-type mice
• upon AOM/DSS induction, levels of intestinal IgG2c antibodies are increased in colon explants, while levels of intestinal IgA, IgG1, IgG2b, and IgG3 antibodies are unaffected
• after immunization of OVA antigen combined with Th1-prone adjuvant, OVA-specific IgG2c antibody production is increased
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• tumor-infiltrating macrophages from MC38-mOVA-inoculated mice exhibit increased in vivo tumor-phagocytosing activity
• IgG purified from OVA-immunized mice with MC38-mOVA induction show more potent bone marrow derived macrophage phagocytosis of antibody-targeted tumor cells
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• IgG purified from OVA-immunized mice with MC38-mOVA induction show more potent bone marrow derived macrophage activation and phagocytosis of antibody-targeted tumor cells
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• purified IgG antibodies from OVA-immunized mice enhances the tumor antigen uptake activities of FLT3L-dendrtic cells
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digestive/alimentary system
• mice treated with azoxymethane/dextran sodium sulfate (AOM/DSS) to induce colitis-associated carcinoma, show reduced weight loss and decreased disease activity index
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mortality/aging
• in the B16-mOVA tumor cell intravenous transplantation model, mice exhibit prolonged survival compared with wild-type mice
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hematopoietic system
• a higher percentage of class-switched IgG2c+ plasma cells are seen in the mesenteric lymph nodes, the colonic lamina propria of AOM/DSS-induced mice and the tumor-draining lymph nodes of MC38 tumor-bearing mice, indicating enhanced plasma cell differentiation in the tumor microenvironment
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• dendritic cells (DCs,) especially CD103+ type I conventional DCs (key antigen-presenting cells that transport antigens to lymphoid structures and prime tumor-specific CD8+ T cells), are elevated in the TME of the MC38 tumor model mice
• however, no differences in tumor-infiltrating macrophages and NK cells are seen in the MC38 tumor model mice
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• in an ovalbumin (OVA) antigen-based immunization model, mice show a higher percentage of OVA-specific IgG2c+ germinal center B cells in the spleen in the tumor microenvironment
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• in an ovalbumin (OVA) antigen-based immunization model, mice show an increase in OVA-specific IgG2c+ memory B cells in the spleen and bone marrow, indicating promotion of class-switched memory B cells in the tumor microenvironment
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• AOM/DSS-induced mice with colorectal cancer exhibit increased infiltration of CD8+ T cells in colon tumor specimens with no differences in CD4+ T cells, NK cells, and macrophages
• infiltration of CD8+ T Cells and IFN-gamma+ CD8+ T cells in the lamina propria and mesenteric lymph nodes is slightly increased in colon tumor specimens of mice with AOM/DSS-induced colorectal cancer
• MC38 tumor-bearing mice show increased amounts of CD8+ T cells within subcutaneous tumor tissues, and especially increased CD44hiCD62LloCD8+ effector T cells, with elevated levels of cytolytic IFN-gamma and granzyme B production, suggesting that tumor-infiltrating CD8+ T cells may help to limit tumor progression
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• MC38 tumor-bearing mice show increased CD44hiCD62LloCD8+ effector T cells
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• in the MC38 transplantation model, mice show elevated amounts of MC38 cell-specific IgG2c antibodies compared to wild-type mice
• B cells from the tumor-draining lymph nodes secrete higher amounts of IgG2c upon restimulation with irradiated MC38 cells than B cells from wild-type mice
• upon AOM/DSS induction, levels of intestinal IgG2c antibodies are increased in colon explants, while levels of intestinal IgA, IgG1, IgG2b, and IgG3 antibodies are unaffected
• after immunization of OVA antigen combined with Th1-prone adjuvant, OVA-specific IgG2c antibody production is increased
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• tumor-infiltrating macrophages from MC38-mOVA-inoculated mice exhibit increased in vivo tumor-phagocytosing activity
• IgG purified from OVA-immunized mice with MC38-mOVA induction show more potent bone marrow derived macrophage phagocytosis of antibody-targeted tumor cells
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• IgG purified from OVA-immunized mice with MC38-mOVA induction show more potent bone marrow derived macrophage activation and phagocytosis of antibody-targeted tumor cells
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homeostasis/metabolism
• mice treated with azoxymethane/dextran sodium sulfate (AOM/DSS) to induce colitis-associated carcinoma, show reduced weight loss, decreased disease activity index, alleviated phenotypes of tumor-associated inflammation, reduced tumor burden, and ameliorated histopathological changes
• mice with AOM/DSS-induced colitis-associated carcinoma show larger tertiary lymphoid structure formation within colon tumors
• tumors from mice with AOM/DSS-induced CAC show increased transcriptional levels of chemokines CXCR5, CXCL12, CXCL13, CCL19, CCL21
• however, no significant difference is seen in the major histocompatibility complex (MHC) and costimulatory molecules CD86 on the cell surface of B cells in the tumor microenvironment, indicating no effect on priming function of B cells to activate T cells
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