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CD4 cells re-educate tumor associated macrophages.

ABSTRACT: Tumor Associated Macrophages (TAMs) are known to release cytokines/chemokines that promote tumor survival and angiogenesis. Little is known, however, about their ability to present tumor antigens to CD4 T cells, nor whether such presentation might switch their tumor supporting function. Here we show that TAMs present tumor antigens to CD4 T cells and that upon antigen recognition, the T cells re-educate the TAMs to produce lower amounts of tumor nurturing proteins and greater amounts of anti-angiogenic proteins. The CD4-educated-TAMs display a gene signature characterized by upregulation of INFgamma esponsive genes that have anti-viral and anti-bacterial function. This phenotypic switch is INF-gamma dependent, and necessary for CD4-mediated tumor rejection. CD4-based immunotherapies could take advantage of this re-education process to improve cancer treatment.

ORGANISM(S): Mus musculus

PROVIDER: GSE40920 | GEO | 2022/08/03

REPOSITORIES: GEO

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Project description:Molecular mechanisms of the cancer cells-macrophages interactions growing in vitro conditions as a co-culture. The five canine mammary cancer cell lines were cultured with monocytes sorted from the canine blood for 72hrs. Then, the cancer cells and macrophages were sorted and the gene expression analysis was conducted. The control for each co-cultured cell line was the same cell line growing as a single culture, whereas the control for the macrophages growing in a co-culture conditions were macrophages growing as a single culture. Solid tumors are comprised of various cells, like cancer cells, resident stromal cells, migratory hemopoietic cells and so on. These cells regulate tumor growth and metastasis. Macrophages are probably the most important element of the interactions within the tumor microenvironment. However, the molecular mechanism how the tumor environment can educate tumor-associated macrophages (TAMs) toward a tumor-promoting phenotype still remains unknown. Moreover, there are no information how the presence of macrophages change the cancer cells phenotype. Exploring the underlying molecular mechanisms of these phenomena was the aim of this study. Solid tumors are comprised of various cells, like cancer cells, resident stromal cells, migratory hemopoietic cells and so on. These cells regulate tumor growth and metastasis. Macrophages are probably the most important element of the interactions within the tumor microenvironment. However, the molecular mechanism how the tumor environment can educate tumor-associated macrophages (TAMs) toward a tumor-promoting phenotype still remains unknown. Moreover, there are no information how the presence of macrophages change the cancer cells phenotype. Exploring the underlying molecular mechanisms of these phenomena was the aim of this study. Dye-swap experiment, each cell line growing in the co-culture conditions was compared to the same cell line growing as a single culture, macrophages growing in the co-culture conditions were compared to the macrophages growing as the single culture.

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CD4 cells re-educate tumor associated macrophages.

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