***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: To analyze the clinical characteristics and prognostic factors in patients with glioma in an academic institute in China . From October 2004 to August 2010 , total 1,285 patients were diagnosed as glioma at the Glioma Center of Beijing Tiantan Hospital . Clinical and molecular pathology features and survival rates were analyzed . The median overall survival ( OS ) times were 78.1 , 37.6 and 14.4 months for low- grade glioma ( WHO grade II ) , anaplastic glioma ( WHO grade III ) and glioblastoma ( WHO grade IV ) , respectively . In patients with low- grade glioma , age , preoperative Karnofsky performance scale ( KPS ) , pathological type , radiotherapy , O6-methylguanine-DNA methyltransferase ( MGMT ) expression and Ki-67 expression , were significantly associated with OS in multivariate analyses ; and preoperative KPS and radiotherapy were significantly associated with progression-free survival ( PFS ) . For anaplastic gliomas , age , preoperative KPS , pathological type , extent of resection , radiotherapy , p53 expression and phosphatase and tensin homolog ( PTEN ) expression were associated with OS . For glioblastomas , age , preoperative KPS , pathology type , extent of resection , radiotherapy and chemotherapy were associated with OS ; and age , gender , preoperative KPS , extent of resection , radiotherapy and chemotherapy were associated with PFS . This is the largest survey for glioma management in China to date . We found significant differences in age , presenting symptoms and the expression of p53 , MGMT , PTEN , and Ki-67 among patients with different types of glioma . Age , preoperative KPS , tumor grade s ,  radiotherapy , chemotherapy and Ki-67 expression were significantly associated with clinical prognosis Background Vascular endothelial growth factor is well known for its angiogenesis potential . The study was performed to determine the possible pro-angiogenic role of magnetic nanoparticles coupled to VEGF in vitro and their capacity to cross an endothelial monolayer . This novel treatment technique for angiogenesis could be potentially useful for therapeutic purpose s using magnetic nanoparticles . Methods Magnetic nanoparticles ( MN ) were synthesized and were conjugated with the vascular endothelial growth factor . The particles were tested in vitro in a 2D to 3D culture system . MN was seeded in different positions in relation to an HUVEC spheroid to assess a preferential migration . To evaluate the MN capacity to cross the endothelial barrier , a confluent monolayer of HUVEC cells was seeded on top of a collagen gel . MN was placed in dissolution on the cell culture media , and the MN position was determined by confocal microscopy for 24 h. Results HUVEC spheroids were able to generate a preferential sprouting depending on the MN position . Meanwhile , there was r and om migration when the MN ’s were placed all over the collagen gel and no sprouting when no MN was added . The trans-endothelial migration capacity of the MN was observed after 20 h in culture in the absence of external stimuli . Conclusion Here we show in vitro angiogenesis following the distribution of the MN conjugated with growth factors . These nanoparticles could be controlled with a magnet to place them in the ischemic area of interest and speed up vascular recovery . Also , MN has potentials to cross endothelium , opening the doors to a possible intravascular and extravascular treatment BACKGROUND Patients with advanced squamous-cell non-small-cell lung cancer ( NSCLC ) who have disease progression during or after first-line chemotherapy have limited treatment options . This r and omized , open-label , international , phase 3 study evaluated the efficacy and safety of nivolumab , a fully human IgG4 programmed death 1 ( PD-1 ) immune-checkpoint-inhibitor antibody , as compared with docetaxel in this patient population . METHODS We r and omly assigned 272 patients to receive nivolumab , at a dose of 3 mg per kilogram of body weight every 2 weeks , or docetaxel , at a dose of 75 mg per square meter of body-surface area every 3 weeks . The primary end point was overall survival . RESULTS The median overall survival was 9.2 months ( 95 % confidence interval [ CI ] , 7.3 to 13.3 ) with nivolumab versus 6.0 months ( 95 % CI , 5.1 to 7.3 ) with docetaxel . The risk of death was 41 % lower with nivolumab than with docetaxel ( hazard ratio , 0.59 ; 95 % CI , 0.44 to 0.79 ; P<0.001 ) . At 1 year , the overall survival rate was 42 % ( 95 % CI , 34 to 50 ) with nivolumab versus 24 % ( 95 % CI , 17 to 31 ) with docetaxel . The response rate was 20 % with nivolumab versus 9 % with docetaxel ( P=0.008 ) . The median progression-free survival was 3.5 months with nivolumab versus 2.8 months with docetaxel ( hazard ratio for death or disease progression , 0.62 ; 95 % CI , 0.47 to 0.81 ; P<0.001 ) . The expression of the PD-1 lig and ( PD-L1 ) was neither prognostic nor predictive of benefit . Treatment-related adverse events of grade 3 or 4 were reported in 7 % of the patients in the nivolumab group as compared with 55 % of those in the docetaxel group . CONCLUSIONS Among patients with advanced , previously treated squamous-cell NSCLC , overall survival , response rate , and progression-free survival were significantly better with nivolumab than with docetaxel , regardless of PD-L1 expression level . ( Funded by Bristol-Myers Squibb ; CheckMate 017 Clinical Trials.gov number , NCT01642004 . ) BACKGROUND Nivolumab was associated with higher rates of objective response than chemotherapy in a phase 3 study involving patients with ipilimumab-refractory metastatic melanoma . The use of nivolumab in previously untreated patients with advanced melanoma has not been tested in a phase 3 controlled study . METHODS We r and omly assigned 418 previously untreated patients who had metastatic melanoma without a BRAF mutation to receive nivolumab ( at a dose of 3 mg per kilogram of body weight every 2 weeks and dacarbazine-matched placebo every 3 weeks ) or dacarbazine ( at a dose of 1000 mg per square meter of body-surface area every 3 weeks and nivolumab-matched placebo every 2 weeks ) . The primary end point was overall survival . RESULTS At 1 year , the overall rate of survival was 72.9 % ( 95 % confidence interval [ CI ] , 65.5 to 78.9 ) in the nivolumab group , as compared with 42.1 % ( 95 % CI , 33.0 to 50.9 ) in the dacarbazine group ( hazard ratio for death , 0.42 ; 99.79 % CI , 0.25 to 0.73 ; P<0.001 ) . The median progression-free survival was 5.1 months in the nivolumab group versus 2.2 months in the dacarbazine group ( hazard ratio for death or progression of disease , 0.43 ; 95 % CI , 0.34 to 0.56 ; P<0.001 ) . The objective response rate was 40.0 % ( 95 % CI , 33.3 to 47.0 ) in the nivolumab group versus 13.9 % ( 95 % CI , 9.5 to 19.4 ) in the dacarbazine group ( odds ratio , 4.06 ; P<0.001 ) . The survival benefit with nivolumab versus dacarbazine was observed across prespecified subgroups , including subgroups defined by status regarding the programmed death lig and 1 ( PD-L1 ) . Common adverse events associated with nivolumab included fatigue , pruritus , and nausea . Drug-related adverse events of grade 3 or 4 occurred in 11.7 % of the patients treated with nivolumab and 17.6 % of those treated with dacarbazine . CONCLUSIONS Nivolumab was associated with significant improvements in overall survival and progression-free survival , as compared with dacarbazine , among previously untreated patients who had metastatic melanoma without a BRAF mutation . ( Funded by Bristol-Myers Squibb ; CheckMate 066 Clinical Trials.gov number , NCT01721772 . ) Background This study evaluated the safety and immune responses to an autologous dendritic cell vaccine pulsed with class I peptides from tumor-associated antigens ( TAA ) expressed on gliomas and overexpressed in their cancer stem cell population ( ICT-107 ) . Methods TAA epitopes included HER2 , TRP-2 , gp100 , MAGE-1 , IL13Rα2 , and AIM -2 . HLA-A1- and /or HLA-A2-positive patients with glioblastoma ( GBM ) were eligible .  Mononuclear cells from leukapheresis were differentiated into dendritic cells , pulsed with TAA peptides , and administered intradermally three times at two-week intervals . Results Twenty-one patients were enrolled with 17 newly diagnosed ( ND-GBM ) and three recurrent GBM patients and one brainstem glioma . Immune response data on 15 newly diagnosed patients showed 33 % responders . TAA expression by qRT-PCR from fresh-frozen tumor sample s showed all patient tumors expressed at least three TAA , with 75 % expressing all six . Correlations of increased PFS and OS with quantitative expression of MAGE1 and AIM -2 were observed , and a trend for longer survival was observed with gp100 and HER2 antigens . Target antigens gp100 , HER1 , and IL13Rα2 were downregulated in recurrent tumors from 4 HLA-A2 + patients . A decrease in or absence of CD133 expression was seen in five patients who underwent a second resection . At a median follow-up of 40.1 months , six of 16 ND-GBM patients showed no evidence of tumor recurrence . Median PFS in newly diagnosed patients was 16.9 months , and median OS was 38.4 months . Conclusions Expression of four ICT-107 targeted antigens in the pre-vaccine tumors correlated with prolonged overall survival and PFS in ND-GBM patients . The goal of targeting tumor antigens highly expressed on glioblastoma cancer stem cells is supported by the observation of decreased or absent CD133 expression in the recurrent areas of gadolinium-enhanced tumors Glioblastoma multiforme ( GBM ) is one of the most aggressive human brain malignancies . Even with optimal treatment , median survival is less than 6 months for patients with recurrent GBM . Immune-based therapies have the potential to improve patient outcome by supplementing st and ard treatment . Expression of human cytomegalovirus ( CMV ) antigens in GBM tissues provides the unique opportunity to target viral antigens for GBM therapy . Here , we report findings of a formal clinical assessment of safety and potential clinical efficacy of autologous CMV-specific T-cell therapy as a consolidative treatment for recurrent GBM . From a total of 19 patients with recurrent GBM , CMV-specific T cells were successfully exp and ed from 13 patients ( 68.4 % ) , 11 of whom received up to four T-cell infusions . Combination therapy based on T-cell infusion and chemotherapy was well tolerated , and we detected only minor adverse events . The overall survival of these patients since first recurrence ranged from 133 to 2,428 days , with a median overall survival of 403 days . Most importantly , 4 of 10 patients that completed the treatment remained progression free during the study period . Furthermore , molecular profiling of CMV-specific T-cell therapy from these patients revealed distinct gene expression signatures , which correlated with their clinical response . Our study suggests that a combination therapy with autologous CMV-specific T cells and chemotherapy is a safe novel treatment option and may offer clinical benefit for patients with recurrent GBM Background The growth and recurrence of several cancers appear to be driven by a population of cancer stem cells ( CSCs ) . Glioblastoma , the most common primary brain tumor , is invariably fatal , with a median survival of approximately 1 year . Although experimental data have suggested the importance of CSCs , few data exist regarding the potential relevance and importance of these cells in a clinical setting . Methods We here present the first seven patients treated with a dendritic cell (DC)-based vaccine targeting CSCs in a solid tumor . Brain tumor biopsies were dissociated into single-cell suspensions , and autologous CSCs were exp and ed in vitro as tumorspheres . From these , CSC-mRNA was amplified and transfected into monocyte-derived autologous DCs . The DCs were aliquoted to 9–18 vaccines containing 107 cells each . These vaccines were injected intradermally at specified intervals after the patients had received a st and ard 6-week course of post-operative radio-chemotherapy . 
    Output:
    
The results revealed that the expression levels of HHLA2 were significantly lower in high‑ grade glioma , as well as glioma with wild‑type isocitrate dehydrogenase , no deletion of 1p/19q and telomerase reverse transcriptase promoter mutation .
Receiver operating characteristic analysis revealed that HHLA2 was a predictor of the neural subtype .
The tumor‑infiltrating immune cell model indicated that HHLA2 was negatively associated with tumor‑associated macrophages .
GO analysis and pathway enrichment analysis revealed that HHLA2‑associated genes were functionally involved in inhibition of neoplasia‑associated processes .
HHLA2 was significantly negatively correlated with certain genes , including interleukin‑10 , transforming growth factor‑β , vascular endothelial growth factor and δ‑like canonical Notch lig and 4 , and other immune checkpoint molecules , including programmed cell death 1 , lymphocyte activating 3 and CD276 .
Survival analysis indicated that high expression of HHLA2 predicted a favorable prognosis .
In conclusion , the present study revealed that upregulation of HHLA2 is significantly associated with a favorable outcome for patients with glioma .
Targeting HHLA2 as an immune stimulator may become a valuable approach for the treatment of glioma in clinical practice