| Gliomas, broadly refers to all neuroepithelium-derived tumor, but it usually refers to the histopathologic tumor derived from various types of glial cells. Glioma is the most common primary tumors in the central nervous system, and the prognosis is poor. Furthermore it is common in young patients, and cause a heavy burden to the entire society and the family. Currently, treatment with glioma requires a comprehensive multidisciplinary treatment, including microscopic surgical excision and postoperative auxiliary chemotherapy. But even with a comprehensive treatment surgery, radiotherapy, chemotherapy, since most of glioma cells insensitive to radiotherapy and chemotherapy, the recurrence and mortality rates remain high. Therefore, to search for other effective alternative or adjunct treatment to improve the prognosis and quality of life in patients with glioma.Argon-helium cryosurgical treatment targeting technology (ultra-low temperature freezer technology) is derived from the United States in recent years. As a partial cryoablation technology, because it can closely monitor the freezing temperature, freezing range. Meanwhile it has the advantages of real-time temperature of the surrounding tissue, and better preservation of more normal brain tissue. And it can treat functional glioma, near important vascular anatomy position glioma or recurrence or residual glioma. Cryoablation can cause membrane rupture, tumor cells antigen massive release, thereby activating the body’s immune system.Now with the tremendous progress in tumor immunology, tumor immunotherapy has achieved encouraging results in the treatment of many solid tumors, especially in malignant melanoma and prostate cancer therapy. Tumor immunotherapy made a surprise effect in a variety of cancer therapy, especially malignant melanoma.Argon-helium cryoablation not only can destroy the local tumor tissue, but also can cause local and systemic immune response, and eliminating the residual or recurrent tumor cells. Studies have reported that cryoablation in addition to the direct physical destruction of tumor cells, but also to promote the maturation of dendritic cells to activate the body’s cellular immune function, to achieve the combination of perfect local minimally invasive therapy with immunotherapy.Argon-helium cryoablation therapy can induce effective immune response, but because cancer patients often have the inhibition of anti-tumor immune response in the body. It is necessary to expand the anti-tumor immune response by immune adjuvant. Reasonable choice of immunomodulatory agents determines whether the applications of cancer vaccine in situ popularized in clinical.Studies have shown that GM-CSF can increase the number of local DCs in tumor, and upregulating the number of DCs in lymphoid organs and activation ratio, can inducing spleen cells to produce specific anti-tumor immune response, and promoting the immune status to converse to Thl response. Currently GM-CSF as GVAX cancer vaccine enhancer, a large number of clinical trials had been conducted in melanoma, prostate cancer, NSCLC and renal cancer and other diseases, the results of these studies show that GM-CSF can be used as an effective immune enhancer to stimulate the body to produce anti-tumor immune response. At the same time, GM-CSF has a stable biological property, and clinical application is safe and effective, is a considerable immunomodulatory agents in the future.In glioma therapy, some patients have residual or recurrent after surgery, no willing to surgical treatment, or in the vicinity of major macro-vascular glioma, because of the protective effect on blood vessels and blood flow avoid vascular injury, for such patients, argon-helium cryoablation can provide an effective alternative. But the technology in gliomas is not mature enough, the lack of the necessary basic research and animal experiments. Also whether GM-CSF can effectively enhance the immune response in glioma-bearing mice, there is no reports currently.To test the hypothesis that combined therapy with cryoablation and GM-CSF for glioma could synergistically improve the survival of glioma-bearing mice and the specific anti-glioma immunity in mice, we tested the validity of this assumption in a murine subcutaneous GL261 glioma model.C57BL/6 mice bearing subcutaneous GL261 glioma were established and divided into 4 groups of no-treatment, GM-CSF injection, cryoablation treatment, and GM-CSF and cryoablation combined treatment (n=20 in each group). Serial immune indicators were detected at sequential time points during treatment. Compared to other groups, in combined treatment group, the tumor size reduced significantly (P< 0.05) and the survival time of tumor-bearing mice extended largely, furthermore DCs were more activated and their numbers were remarkably upregulated, the secretion of IFN-gamma from Thl cells of mice spleen was increased, and the cytolytic activity of CD8+ CTLs produced a more significant cytotoxic effect on GL261 glioma cells (P <0.05 for all). Furthermore, these changes reached the peak on the 7th day after treatment, then gradually reduced, until the 21st day these changes were higher than that of pre-treatment (P<0.05). It is concluded that combined therapy with argon-helium cryoablation and GM-CSF could significantly reduce the tumor size and prolong the survival time of tumor-bearing mice, and synergistically enhance the activation of DCs and induce robust tumor-specific immunologic response in glioma-bearing mice. |
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