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Int J Oncol ; 53(4): 1580-1590, 2018 Oct.
Article in English | MEDLINE | ID: mdl-30066851

ABSTRACT

Increased neutrophil counts are a hallmark of a poor prognosis for cancer. We previously reported that KRAS promoted tumorigenesis and increased neutrophil counts in a mouse peritoneal cancer model. In the current study, we evaluated the role of increased neutrophils in cancer progression, as well as their influence on the intraperitoneal microenvironment. A mouse peritoneal cancer model was established using the KRAS-transduced mouse ovarian cancer cell line, ID8-KRAS. Neutrophil function was assessed by neutrophil depletion in ID8-KRAS mice. Neutrophil depletion markedly accelerated tumor formation; this was accompanied by an increase in interleukin-6 concentrations in ascites. Neutrophil depletion significantly decreased the amount of local and systemic CD8+ T cells, while increasing the amount of local CD4+ T cells, accompanied by an increased amount of monocytic myeloid-derived suppressor cells (M-MDSCs) and regulatory T cells (Tregs) (P<0.05). The roles of peritoneal neutrophils (PENs) in CD8+ T cell activation were assessed in vitro. PENs of ID8-KRAS mice had a strong potential to enhance T cell proliferation with a higher expression of the T cell costimulatory molecules OX40 ligand (OX40L) and 4-1BB ligand (4-1BBL), as compared with peripheral blood neutrophils (PBNs). These findings suggest that neutrophils recruited into the KRAS-induced tumor microenvironment (TME) have antitumor properties with the potential to modulate the numbers of M-MDSCs and Tregs and activate CD8+ T cells through T cell costimulatory molecules.


Subject(s)
Adaptive Immunity , Neutrophils/immunology , Ovarian Neoplasms/immunology , Proto-Oncogene Proteins p21(ras)/immunology , Tumor Microenvironment/immunology , Animals , Cell Line, Tumor , Disease Progression , Female , Humans , Leukocyte Count , Mice , Mice, Inbred C57BL , Mutation , Myeloid-Derived Suppressor Cells/immunology , Ovarian Neoplasms/blood , Ovarian Neoplasms/genetics , Peritoneal Cavity/cytology , Proto-Oncogene Proteins p21(ras)/genetics , T-Lymphocytes/immunology , Transduction, Genetic , Xenograft Model Antitumor Assays
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