ABSTRACT
Glioblastoma (GBM) is a hypervascular and aggressive primary malignant tumor of the central nervous system. Recent investigations showed that traditional therapies along with antiangiogenic therapies failed due to the development of post-therapy resistance and recurrence. Previous investigations showed that there were changes in the cellular and metabolic compositions in the tumor microenvironment (TME). It can be said that tumor cell-directed therapies are ineffective and rethinking is needed how to treat GBM. It is hypothesized that the composition of TME-associated cells will be different based on the therapy and therapeutic agents, and TME-targeting therapy will be better to decrease recurrence and improve survival. Therefore, the purpose of this study is to determine the changes in the TME in respect of T-cell population, M1 and M2 macrophage polarization status, and MDSC population following different treatments in a syngeneic model of GBM. In addition to these parameters, tumor growth and survival were also studied following different treatments. The results showed that changes in the TME-associated cells were dependent on the therapeutic agents, and the TME-targeting therapy improved the survival of the GBM bearing animals. The current GBM therapies should be revisited to add agents to prevent the accumulation of bone marrow-derived cells in the TME or to prevent the effect of immune-suppressive myeloid cells in causing alternative neovascularization, the revival of glioma stem cells, and recurrence. Instead of concurrent therapy, a sequential strategy would be better to target TME-associated cells.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/pharmacology , Brain Neoplasms/drug therapy , Glioblastoma/drug therapy , Animals , Brain Neoplasms/immunology , Brain Neoplasms/metabolism , Brain Neoplasms/pathology , Cell Line, Tumor , Disease Models, Animal , Female , Glioblastoma/immunology , Glioblastoma/metabolism , Glioblastoma/pathology , Immunotherapy/methods , Macrophages/drug effects , Macrophages/immunology , Macrophages/pathology , Male , Mice , Mice, Knockout , Mice, Nude , Myeloid Cells/drug effects , Myeloid Cells/immunology , Myeloid Cells/pathology , Pilot Projects , Receptors, Granulocyte-Macrophage Colony-Stimulating Factor/genetics , Receptors, Granulocyte-Macrophage Colony-Stimulating Factor/metabolism , Tumor Microenvironment/drug effects , Tumor Microenvironment/immunologyABSTRACT
73-year-old man with ulcerative colitis was diagnosed with Campylobacter jejuni prosthetic knee infection. No preceding gastrointestinal illness was reported. Joint aspirate and operative cultures were negative; however, blood cultures were positive for Campylobacter jejuni. The role of ulcerative colitis in inducing bacteremia and subsequent prosthetic joint infection is discussed.
