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@#Gliomas are the most common primary malignant tumors in the central nervous system，and more than half of them are WHO grade IV glioblastomas. Even if surgery，concurrent chemoradiotherapy and adjuvant chemotherapy were applied，median survival of GBM patients is still only 14.2 months. Immunosuppression is an important feature of malignant glioma. Immunotherapy which reverse immunosuppression may be the most promising way to improve the treatment effect of glioma patients in recent years. This article reviews the recent progress of glioma immunotherapy and the research progress of regulatory T cells（Treg）and glucocorticoid-induced tumor necrosis factor receptor（GITR）in the glioma microenvironment. We hope this article will provides new research ideas for glioma immunotherapy.
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BACKGROUND@#Cerebrospinal fluid (CSF) has been demonstrated as a better source of circulating tumor DNA (ctDNA) than plasma for brain tumors. However, it is unclear whether whole exome sequencing (WES) is qualified for detection of ctDNA in CSF. The aim of this study was to determine if assessment of ctDNA in CSF by WES is a feasible approach to detect genomic alterations of glioblastoma.@*METHODS@#CSFs of ten glioblastoma patients were collected pre-operatively at the Department of Neurosurgery, Sun Yat-sen University Cancer Center. ctDNA in CSF and genome DNA in the resected tumor were extracted and subjected to WES. The identified glioblastoma-associated mutations from ctDNA in CSF and genome DNA in the resected tumor were compared.@*RESULTS@#Due to the ctDNA in CSF was unqualified for exome sequencing for one patient, nine patients were included into the final analysis. More glioblastoma-associated mutations tended to be detected in CSF compared with the corresponding tumor tissue samples (3.56 ± 0.75 vs. 2.22 ± 0.32, P = 0.097), while the statistical significance was limited by the small sample size. The average mutation frequencies were similar in CSF and tumor tissue samples (74.1% ± 6.0% vs. 73.8% ± 6.0%, P = 0.924). The R132H mutation of isocitrate dehydrogenase 1 and the G34V mutation of H3 histone, family 3A (H3F3A) which had been reported in the pathological diagnoses were also detected from ctDNA in CSF by WES. Patients who received temozolomide chemotherapy previously or those whose tumor involved subventricular zone tended to harbor more mutations in their CSF.@*CONCLUSION@#Assessment of ctDNA in CSF by WES is a feasible approach to detect genomic alterations of glioblastoma, which may provide useful information for the decision of treatment strategy.
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Objective To explore whether aggressive treatment of primary focus can benefit nonsmall cell lung cancer(NSCLC)patients with synchronous brain metastasis,and search the appropriate treatment protocols.Methods The clinical data of 19 NSCLC patients with synchronous brain metastasis,received treatment at our Cancer Center from January 2000 to January 2009,were reviewed; their treatments and survival statuses were analyzed.Results Median survival time of these patients was 14.5 months; the 1-year survival rate was 52.6％,and 2-year survival rate was 17.5％.Patients had different survival rates when different treatments were given to the primary focus,and significant difference was noted(x2=10.532,P=0.005); after neurosurgical intervention,patients underwent thoracic operation and chemotherapy(24.9 months)had a significantly longer survival time than those underwent chemotherapy(14.5 months)or palliative therapy(5.4 months,P＜0.05).The survival time of patients with single metastases was 16.3 months,and that of those with multiple metastases was 5.4 months; and significant difference was noted between them(P＜0.05).Conclusion Aggressive therapy including neurosurgical intervention,pulmonary resection and chemotherapy should be recommended for NSCLC patients with synchronous brain metastasis,especially those with single brain metastasis.
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Objective To explore the relationship between T lymphocyte subsets and both glioma malignancy and its prognosis, and determine a clinical immunologic index for evaluating preoperative glioma malignancy and its prognosis. Methods The data of 117 inpatients with primary intracranial tumors, including glioma (n=85) and meningioma (n=32), were retrospectively analyzed. Fluorescence-activated cell sorting (FACS) analysis was performed to detect the preoperative contents of T lymphocyte subsets on 32 patients with meningioma and patients with glioma, including 45 high-grade glioma (WHO, grade Ⅲ-Ⅳ) and 40 low-grade glioma (WHO, grade Ⅰ -Ⅱ); and then the differences of their immunologic indexes were analyzed. Based on the detection result of T lymphocyte subsets, patients with glioma were divided into two groups: CD4~+CD8~+<1 and CD4~+CD8~+>1. Follow-up for 3-5 years was performed and the survival difference of these two groups was analyzed. Results Patients with high-grade glioma showed a decreased ratio of CD4~+CD8~+ and an increased value of CD8~+ with significant difference as compared with patients with low-grade glioma (P<0.05); patients with high-grade glioma showed a decreased ratio of CD4~+CD8~+, and an increased value of CD8~+ with statistical significance compared with patients with meningioma (P <0.05); patients with low-grade glioma showed a decreased ratio of CD4~+CD8~+ with statistical significance compared with the patients with meningioma (P<0.05). Patients with glioma showed a decreased ratio of CD4~+CD8~+ and CD4~+, and an increased CD8~+ with statistical significance compared with patients with meningioma (P<0.05). After follow-up for 3-5 years, 48 patients with glioma was found in the CD4~+CD8~+>1 group with 21 death (43.8%) and 31 months as a median survival time; 37 patients with glioma was found in the CD4~+CD8~+<1 group with 23 death (62.2%) and 16 months as a median survival time. The Kaplan-Meier survival curves were analyzed with statistical significance (P<0.05). Conclusion The prognosis is poor in patients with low ratio of CD4~+CD8~+. The preoperative level of T lymphocyte subsets in peripheral blood, correlated to the glioma malignancy, can be considered as an index to evaluate the glioma malignancy and the prognosis in patients with glioma.