digestive/alimentary system
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• tamoxifen-treated mice develop colorectal cancer
• treatment with a broad-spectrum antibiotic cocktail for only one week results in smaller tumors while not affecting tumor number or burden
• in tamoxifen-treated mice, approximately 60% of IL-17 producing cells within the tumor are gamma-delta T cells whereas T helper 17 (TH17) cells constitute only 20%
• tumor-infiltrating gamma-delta T cells show clonal expansions; the expanded clones found in tumor areas are primarily Vgamma6+Vdelta1+ clones (Trgv6 and Trdv4 rearrangements) which are rarely seen in nontumor areas and the increase of Vgamma6+ cells is at the expense of decreased Vgamma7+ gamma-delta T cells in tumor areas
• treatment with a broad-spectrum antibiotic cocktail to deplete microbiota leads to a decrease in intratumoral Vgamma6+ gamma-delta T cells but does not affect Vgamma4+ cells
• treatment with anti-TCRgamma-delta blocking (nondepleting) antibodies for 2 weeks starting 7 days before tamoxifen administration has no effect on tumor number or size, gamma-delta/alpha-beta ratio, or frequencies of CD8alpha+ PD-1+, and IL-17- and IFN-gamma-producing gamma-delta T cells or CD4+ T cell proliferation
• treatment with anti-TCRgamma-delta blocking antibody for 2 weeks starting 3 weeks after initial tamoxifen treatment leads to a decrease in tumor size and burden but does not change tumor number, decrease in both PD-1+- and IL-17-producing gamma-delta T cells in tumor areas
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• mice show a sharp decrease in gut microbial diversity as well as broad changes in bacterial composition that can be detected as early as 2 weeks after tamoxifen administration
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hematopoietic system
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• tamoxifen-treated mice show a decreased frequency of CD8alpha+ gamma-delta T cells in colonic tissue
• mice treated with a broad-spectrum antibiotic cocktail show increased frequency of CD8alpha+ gamma-delta T cells in both nontumor and tumor sites
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• tamoxifen-treated mice show accumulation of gamma-delta T cells expressing IL-17 and PD-1 in colonic tissue
• the frequency of gamma-delta T cells producing IFN-gamma and IL-17 is increased among tumor-infiltrating lymphocytes of tamoxifen-treated mice
• mice treated with a broad-spectrum antibiotic cocktail show reduced frequency of IL-17- and PD-1 expressing gamma-delta T cells, primarily within the Vgamma6+ subset
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immune system
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• tamoxifen-treated mice show a decreased frequency of CD8alpha+ gamma-delta T cells in colonic tissue
• mice treated with a broad-spectrum antibiotic cocktail show increased frequency of CD8alpha+ gamma-delta T cells in both nontumor and tumor sites
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• tamoxifen-treated mice show accumulation of gamma-delta T cells expressing IL-17 and PD-1 in colonic tissue
• the frequency of gamma-delta T cells producing IFN-gamma and IL-17 is increased among tumor-infiltrating lymphocytes of tamoxifen-treated mice
• mice treated with a broad-spectrum antibiotic cocktail show reduced frequency of IL-17- and PD-1 expressing gamma-delta T cells, primarily within the Vgamma6+ subset
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neoplasm
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• tamoxifen-treated mice develop colorectal cancer
• treatment with a broad-spectrum antibiotic cocktail for only one week results in smaller tumors while not affecting tumor number or burden
• in tamoxifen-treated mice, approximately 60% of IL-17 producing cells within the tumor are gamma-delta T cells whereas T helper 17 (TH17) cells constitute only 20%
• tumor-infiltrating gamma-delta T cells show clonal expansions; the expanded clones found in tumor areas are primarily Vgamma6+Vdelta1+ clones (Trgv6 and Trdv4 rearrangements) which are rarely seen in nontumor areas and the increase of Vgamma6+ cells is at the expense of decreased Vgamma7+ gamma-delta T cells in tumor areas
• treatment with a broad-spectrum antibiotic cocktail to deplete microbiota leads to a decrease in intratumoral Vgamma6+ gamma-delta T cells but does not affect Vgamma4+ cells
• treatment with anti-TCRgamma-delta blocking (nondepleting) antibodies for 2 weeks starting 7 days before tamoxifen administration has no effect on tumor number or size, gamma-delta/alpha-beta ratio, or frequencies of CD8alpha+ PD-1+, and IL-17- and IFN-gamma-producing gamma-delta T cells or CD4+ T cell proliferation
• treatment with anti-TCRgamma-delta blocking antibody for 2 weeks starting 3 weeks after initial tamoxifen treatment leads to a decrease in tumor size and burden but does not change tumor number, decrease in both PD-1+- and IL-17-producing gamma-delta T cells in tumor areas
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