ABSTRACT
Malignant gliomas, particularly glioblastoma multiforme (GBM) tumors, are very difficult to treat by conventional approaches. Although most of the tumor mass can be removed by surgical resection, radiotherapy, and chemotherapy, it eventually recurs. There is growing evidence that cancer stem cells (CSCs) play an important role in tumor recurrence. These stem cells are radioresistant and chemoresistant. The most commonly used tumor marker for CSCs is CD133. The amount of CSC component is closely correlated with tumor malignancy grading. Isolating, identifying, and treating CSCs as the target is crucial for treating malignant gliomas. CSC-associated vascular endothelial growth factor (VEGF) promotes tumor angiogenesis, tumor hemorrhage, and tumor infiltration. Micro-RNA (miRNA) plays a role in CSC gene expression, which may regulate oncogenesis or suppression to influence tumor development or progression. The antigenesis of CSCs and normal stem cells may be different. The CSCs may escape the T-cell immune response. Identifying a new specific antigen from CSCs for vaccine treatment is a key point for immunotherapy. On the other hand, augmented treatment with radiosensitizer or chemosensitizer may lead to reduction of CSCs and lead to CSCs being vulnerable to radiotherapy and chemotherapy. The control of signaling pathway and cell differentiation to CSC growth is another new hope for treatment of malignant gliomas. Although the many physiological behavioral differences between CSCs and normal stem cells are unclear, the more we know about these differences the better we will be able to treat CSCs effectively.
Subject(s)
Antigens, CD/metabolism , Glioma/therapy , Glycoproteins/metabolism , Neoplastic Stem Cells/physiology , Peptides/metabolism , AC133 Antigen , Glioma/pathology , Humans , Immunotherapy , MicroRNAs/metabolism , MicroRNAs/physiology , Neoplastic Stem Cells/cytology , Neoplastic Stem Cells/metabolism , Radiation-Sensitizing Agents/therapeutic use , Signal TransductionABSTRACT
Immunotherapy is a new light of hope for the treatment of malignant gliomas. The brain is no longer believed to be an immunologically privileged organ. The major advantage of immunotherapy is the tumor-specific cytotoxic effect on the tumor cells with minimal side effects. Autologous dendritic cells (DCs)-based immunotherapy is a promising and feasible method. DCs are the most potent antigen-presenting cells (APCs). DCs prime T lymphocytes by epitopic major histocompatibility (MHC) class I and II for CD8(+) cytotoxic T lymphocytes (CTLs) and CD4(+) T helper cells, respectively. From the tissue specimen examination after DCs-based immunotherapy, CD8(+) CTLs have replaced T regulatory cells (Tregs) as the major dominant tissue infiltrating lymphocytes (TILs). CD8(+) CTLs play a key role in the tumor response, which may also be effective against cancer stem cells. DCs themselves also produce many cytokines including interferon-gamma and interleukin (IL-2) to kill the tumor cells. From the preliminary better outcomes in the literature for malignant gliomas, DC-based immunotherapy may improve tumor response by increasing the survival rate and time. It is recommended that DC-based immunotherapy is applied as soon as possible with conjunctive radiotherapy and chemotherapy. Malignant gliomas have heterogeneity of tissue-associated antigens (TAAs). To find universal common antigens through different kinds of tumor culture may be the essential issue for tumor vaccine development in the future.
