Genetic basis of maize stalk strength decoded via linkage and association mapping.

Stalk lodging is a severe problem that limits maize production worldwide, although little attention has been given to its genetic basis. Here we measured rind penetrometer resistance (RPR), an effective index for stalk lodging, in a multi-parent population of 1948 recombinant inbred lines (RILs) and an association population of 508 inbred lines (AMP508). Linkage and association mapping identified 53 and 29 single quantitative trait loci (QTLs) and 50 and 19 pairs of epistatic interactions for RPR in the multi-parent population and AMP508 population, respectively. Phenotypic variation explained by all identified epistatic QTLs (up to ~5%) was much less than that explained by all single additive QTLs (up to ~33% in the multi-parent population and ~ 60% in the AMP508 population). Among all detected QTLs, only eight single QTLs explained >10% of phenotypic variation in single RIL populations. Alleles that increased RPR were enriched in tropical/subtropical (TST) groups from the AMP508 population. Based on genome-wide association studies in both populations, we identified 137 candidate genes affecting RPR, which were assigned to multiple biological processes, such as the biosynthesis of cell wall components. Sixty-six candidate genes were cross-validated by multiple methods or populations. Most importantly, 23 candidate genes were upregulated or downregulated in high-RPR lines relative to low-RPR lines, supporting the associations between candidate genes and RPR. These findings reveal the complex nature of the genetic basis underlying RPR and provide loci or candidate genes for developing elite varieties that are resistant to stalk lodging via molecular breeding.

Linkage and association mapping in multi-parental populations reveal the genetic basis of carotenoid variation in maize kernels.

Carotenoids are indispensable to plants and critical components of the human diet. The carotenoid metabolic pathway is conserved across plant species, but our understanding of the genetic basis of carotenoid variation remains limited for the seeds of most cereal crops. To address this issue, we systematically performed linkage and association mapping for eight carotenoid traits using six recombinant inbred line (RIL) populations. Single linkage mapping (SLM) and joint linkage mapping (JLM) identified 77 unique additive QTLs and 104 pairs of epistatic QTLs. Among these QTLs, we identified 22 overlapping hotspots of additive and epistatic loci, highlighting the important contributions of some QTLs to carotenoid levels through additive or epistatic mechanisms. A genome-wide association study based on all RILs detected 244 candidate genes significantly associated with carotenoid traits, 23 of which were annotated as carotenoid pathway genes. Effect comparisons suggested that a small number of loci linked to pathway genes have substantial effects on carotenoid variation in our tested populations, but many loci not associated with pathway genes also make important contributions to carotenoid variation. We identified ZmPTOX as the causal gene for a QTL hotspot (Q10/JLM10/GWAS019); this gene encodes a putative plastid terminal oxidase that produces plastoquinone-9 used by two enzymes in the carotenoid pathway. Natural variants in the promoter and second exon of ZmPTOX were found to alter carotenoid levels. This comprehensive assessment of the genetic mechanisms underlying carotenoid variation establishes a foundation for rewiring carotenoid metabolism and accumulation for efficient carotenoid biofortification.

Recent advances and future challenges of tumor vaccination therapy for recurrent glioblastoma.

Glioblastoma (GBM) is the most malignant CNS tumor with a highest incidence rate, and most patients would undergo a recurrence. Recurrent GBM (rGBM) shows an increasing resistance to chemotherapy and radiotherapy, leading to a significantly poorer prognosis and the urgent need for novel treatments. Immunotherapy, a rapidly developing anti-tumor therapy in recent years, has shown its potential value in rGBM. Recent studies on PD-1 immunotherapy and CAR-T therapy have shown some efficacy, but the outcome was not as expected. Tumor vaccination is the oldest approach of immunotherapies, which has returned to the research focus because of the failure of other strategies and subversive understanding of CNS. The isolation effect of blood brain barrier and the immunosuppressive cell infiltration could lead to resistance existing in all phases of the anti-tumor immune response, where novel tumor vaccines have been designed to overcome these problems through new tumor antigenic targets and regulatory of the systematic immune response. In this review, the immunological characteristics of CNS and GBM would be discussed and summarized, as well as the mechanism of each novel tumor vaccine for rGBM. And through the review of completed early-phase studies and ongoing large-scale phase III clinical trials, evaluation could be conducted for potential immune response, biosecurity and initial clinical outcome, which further draw a panorama of this vital research field and provide some deep thoughts for the prospective tendency of vaccination strategy. Video Abstract.

Goethite Formed in the Periplasmic Space of Pseudomonas sp. JM-7 during Fe Cycling Enhances Its Denitrification in Water.

Denitrification-driven Fe(II) oxidation is an important microbial metabolism that connects iron and nitrogen cycling in the environment. The formation of Fe(III) minerals in the periplasmic space has a significant effect on microbial metabolism and electron transfer, but direct evidence of iron ions entering the periplasm and resulting in periplasmic mineral precipitation and electron conduction properties has yet to be conclusively determined. Here, we investigated the pathways and amounts of iron, with different valence states and morphologies, entering the periplasmic space of the denitrifier Pseudomonas sp. JM-7 (P. JM-7), and the possible effects on the electron transfer and the denitrifying ability. When consistently provided with Fe(II) ions (from siderite (FeCO3)), the dissolved Fe(II) ions entered the periplasmic space and were oxidized to Fe(III), leading to the formation of a 25 nm thick crystalline goethite crust, which functioned as a semiconductor, accelerating the transfer of electrons from the intracellular to the extracellular matrix. This consequently doubled the denitrification rate and increased the electron transport capacity by 4-30 times (0.015-0.04 µA). However, as the Fe(II) concentration further increased to above 4 mM, the Fe(II) ions tended to preferentially nucleate, oxidize, and crystallize on the outer surface of P. JM-7, leading to the formation of a densely crystallized goethite layer, which significantly slowed down the metabolism of P. JM-7. In contrast to the Fe(II) conditions, regardless of the initial concentration of Fe(III), it was challenging for Fe(III) ions to form goethite in the periplasmic space. This work has shed light on the likely effects of iron on environmental microorganisms, improved our understanding of globally significant iron and nitrogen geochemical cycles in water, and expanded our ability to study and control these important processes.

Molecular landscape of IDH-mutant astrocytoma and oligodendroglioma grade 2 indicate tumor purity as an underlying genomic factor.

BACKGROUND: IDH-mutant astrocytoma and oligodendroglioma have an indolent natural history and are recognized as distinct entities of neoplasms. There is little knowledge on the molecular differences between IDH-mutant astrocytoma and oligodendroglioma grade 2. Therefore, we investigated the multiomics and clinical data regarding these two types of tumors. METHOD: In silico analyses were performed around mRNA, somatic mutations, copy number alternations (CNAs), DNA methylation, microRNA (miRNA), epigenetics, immune microenvironment characterization and clinical features of the two types of gliomas. A diagnostic model incorporating tumor purity was further established using machine learning algorithms, and the predictive value was evaluated by receiver operative characteristic curves. RESULTS: Both types of gliomas shared chromosomal instability, and astrocytomas exhibited increased total CNAs compared to oligodendrogliomas. Oligodendrogliomas displayed distinct chromosome 4 (chr 4) loss, and subtyping of chr 7 gain/chr 4 loss (+ 7/- 4) presented the worst survival (P = 0.004) and progression-free interval (PFI) (P < 0.001). In DNA damage signatures, oligodendroglioma had a higher subclonal genome fraction (P < 0.001) and tumor purity (P = 0.001), and astrocytoma had a higher aneuploidy score (P < 0.001). Furthermore, astrocytomas exhibited inflamed immune cell infiltration, activated T cells and a potential response to immune checkpoint inhibitors (ICIs), while oligodendrogliomas were more homogeneous with increased tumor purity and decreased aggression. The tumor purity-involved diagnostic model exhibited great accuracy in identifying astrocytoma and oligodendroglioma. CONCLUSION: This study addresses the similarities and differences between IDH-mutant astrocytoma and oligodendroglioma grade 2 and facilitates a deeper understanding of their molecular features, immune microenvironment, tumor purity and prognosis. The diagnostic tool developed using machine learning may offer support for clinical decisions.

Comparative efficacy and safety of therapeutics for elderly glioblastoma patients: A Bayesian network analysis.

Optimal management strategies for elderly glioblastoma (GBM) patients remain elusive. Overall survival (OS) and progression-free survival (PFS) in elderly newly diagnosed GBM (ndGBM) patients were analyzed with random-effects Bayesian network meta-analysis with the estimated hazard ratio (HR) with a 95% confidence interval (95% CrI). In addition, OS, PFS and adverse event (AE) data on ndGBM and recurrent GBM (rGBM) were assessed. Seventeen eligible trials with 12 on ndGBM and 5 on rGBM were identified. For the improvements it induced in the OS of elderly ndGBM patients, tumor treating field (TTF) + temozolomide (TMZ) (HR: 0.11, 95% CrI: 0.02-0.67 vs. supportive care (SPC)) ranked first, followed by TMZ + hyperfractionated radiotherapy (HFRT) (HR: 0.17, 95% CrI: 0.03-0.95 vs. SPC). For the improvements it induced in the PFS of elderly ndGBM patients, bevacizumab (BEV) + HFRT ranked first, followed by TMZ + HFRT. TMZ was observed to be more effective in O6-methylguanine-DNA-methyltransferase (MGMT) promoter-methylated ndGBM patients than HFRT and standard radiotherapy (STRT). For elderly rGBM patients, the treatments included were comparable. The rates of other neurological symptoms (16.1%) and lymphocytopenia (10.4%) were higher in ndGBM patients; lymphocytopenia (10.3%) and infection (8.1%) were higher in rGBM patients among the ≥ 3 grade AEs. TMZ-related AEs should be further considered. In conclusion, TTF + adjuvant TMZ and TMZ + HFRT are most likely to be recommended for elderly ndGBM patients. No best treatment for rGBM in elderly patients is illustrated. TMZ is identified to be more effective in elderly ndGBM patients with methylated MGMT status; however, AEs associated with TMZ-related therapy should be well considered and managed.

Effect of Fibular Osteotomy with Joint Debridement on Pain and Range of Motion in Patients with Knee Osteoarthritis.

Objective: The aim of this study was to attempt to evaluate the effect of fibular osteotomy (FO) with joint debridement compared with arthroscopic debridement in terms of the degree of pain and range of motion in patients with knee osteoarthritis (KOA). Methods: From August 2018 to February 2020, our hospital admitted 88 patients with KOA to this prospective study. They were randomly divided into 2 groups: the FO group (44 patients) received an FO with joint debridement and the control group (44 patients) were given simple arthroscopic debridement. Detailed data regarding clinical symptoms, knee joint function and degree of pain were collected and recorded before and 3 and 6 months after surgery in order to compare the patients' quality of life (QoL), related nerve injury, delayed union, wound infection and other complications in the 2 groups. Results: No significant difference were found regarding pre-operative clinical symptoms in the 2 groups (P > .05). However, 3 months and 6 months after surgery, the clinical symptoms in the FO group were highly associated with lower outcomes compared with the control group (P < .05). Although there were no significant differences in terms of knee function, degree of pain or QoL between the 2 groups before surgery (P > .05), there was a superior beneficial effect on the above symptoms observed in the FO group compared with the control group at 3 and 6 months. In this study, no complications such as nerve injury, delayed healing or wound infection occurred in either group. Conclusion: The significant improvements in terms of clinical symptoms, pain and range of motion were observed following FO with joint debridement in patients with KOA. Hence, this approach may be valid for broad clinical application.

Systematic identification, development, and validation of prognostic biomarkers involving the tumor-immune microenvironment for glioblastoma.

Gliomas are infiltrative neoplasms with a highly invasive nature. Due to its distinct genomic, genetic and epigenetic features, the immune prognostic signature (IPS) and immune microenvironment of glioblastoma (GBM) merit further research. We aimed to explore prognosis-related immune genes and develop an IPS model for predicting prognosis in GBM. RNA-sequencing data, as well as clinical information, from The Cancer Genome Atlas (TCGA) and Chinese Glioma Genome Atlas (CGGA) public cohorts were analyzed. To develop the IPS, least absolute shrinkage and selection operator (LASSO) Cox analysis was performed for immune-related genes that were differentially expressed between GBM and normal tissues. Then, interaction effects of the IPS on the immune microenvironment were systematically analyzed; the precise prognostic model was developed based on the IPS and clinical data and was then further validated. A total of 21 immune prognostic genes were identified based on GBM microenvironment status. An 8-gene IPS was established, and the GBM patients were effectively stratified into low- and high-risk groups in the TCGA cohort as a training set. Univariate and multivariate Cox analyses revealed that IPS was an independent prognostic factor, and the prognostic performance of individual IPS genes was systematically illustrated. In addition, a comprehensive and novel nomogram model was initially established to estimate overall survival in TCGA-GBM patients, and high-risk patients had higher levels of dendritic cell and neutrophil infiltration. Furthermore, the nomogram model was developed and validated in the CGGA validation set. The low-risk IPS was linked to a stronger response to anti-PD-L1 immunotherapy and clinical advantages in the IMvigor210 cohort. This novel IPS with promising biomarkers classifies GBM patients into subgroups with distinct clinical outcomes and immunophenotypes. Our findings and this resource may help to characterize the immune microenvironment, inform cancer immunotherapy and facilitate the development of precision immuno-oncology.

Genome-Wide Association Analyses Reveal the Importance of Alternative Splicing in Diversifying Gene Function and Regulating Phenotypic Variation in Maize.

Alternative splicing (AS) enhances transcriptome diversity and plays important roles in regulating plant processes. Although widespread natural variation in AS has been observed in plants, how AS is regulated and contribute to phenotypic variation is poorly understood. Here, we report a population-level transcriptome assembly and genome-wide association study to identify splicing quantitative trait loci (sQTLs) in developing maize (Zea mays) kernels from 368 inbred lines. We detected 19,554 unique sQTLs for 6570 genes. Most sQTLs showed small isoform usage changes without involving major isoform switching between genotypes. The sQTL-affected isoforms tend to display distinct protein functions. We demonstrate that nonsense-mediated mRNA decay, microRNA-mediated regulation, and small interfering peptide-mediated peptide interference are frequently involved in sQTL regulation. The natural variation in AS and overall mRNA level appears to be independently regulated with different cis-sequences preferentially used. We identified 214 putative trans-acting splicing regulators, among which ZmGRP1, encoding an hnRNP-like glycine-rich RNA binding protein, regulates the largest trans-cluster. Knockout of ZmGRP1 by CRISPR/Cas9 altered splicing of numerous downstream genes. We found that 739 sQTLs colocalized with previous marker-trait associations, most of which occurred without changes in overall mRNA level. Our findings uncover the importance of AS in diversifying gene function and regulating phenotypic variation.

A Bayesian network meta-analysis regarding the comparative efficacy of therapeutics for ALK-positive, brain metastatic non-small cell lung cancer.

More clinical evidence is needed regarding the ranking priority of interventions for ALK-positive, brain metastatic (BM) non-small cell lung cancer (NSCLC). Eligible randomized controlled trials (RCTs) were identified. Progression-free survival (PFS), objective response rate (ORR) and overall survival (OS) for the intended populations were analyzed with random effects, Bayesian network meta-analysis with the estimated hazard ratio (HR) and odds ratio (OR) with 95% credible interval (95% CrIs). We included 11 RCTs (2687 NSCLC and 991 BM patients) investigating 7 treatments and 5 medication classes. For PFS for BM patients, lorlatinib (hazard ratio (HR): 0.01, 95% CrI: 0.001-0.12), alectinib (HR: 0.05, 95% CrI: 0.01-0.21) and brigatinib (HR: 0.07, 95% CrI: 0.007-0.76) were top-ranking individual treatments; for ORR for BM patients, brigatinib, lorlatinib and alectinib were top-ranking treatments. For PFS for all NSCLC patients, the top-ranking individual treatments were lorlatinib (HR: 0.05, 95% CrI: 0.02-0.13), alectinib (HR: 0.09, 95% CrI: 0.05-0.18) and brigatinib (HR: 0.11, 95% CrI: 0.05-0.28). For OS for all NSCLC patients, we found that no individual treatments were superior to chemotherapy, whereas the following top-ranking interventions were alectinib (HR: 0.29, 95% CrI: 0.03-1.68), lorlatinib (HR: 0.41, 95% CrI: 0.04-4.13), and ceritinib (HR: 0.63, 95% CrI: 0.10-4.25). The results of individual treatments and medication classes were similar. Data were limited in regard to subgroup analyses and adverse events of BM patients. Lorlatinib has the most statistical superiority for BM patients, but ORR differences between third- and second-generation inhibitors are not obvious. All things considered, alectinib is recommended as first-line treatment, followed by lorlatinib, especially after developing drug resistance to alectinib.

Repair of Lafosse I subscapularis injury adds no additional value in anterosuperior rotator cuff injury.

BACKGROUND: The study aimed to explore the additional value of repair of Lafosse I subscapularis injury compared with debridement in anterosuperior rotator cuff injury. METHODS: The prospective study was conducted on a total of 41 patients with supraspinatus tendon tear combined with Lafosse I subscapularis injury. Eighteen patients were divided into the repair group and 23 patients were divided into the non-repair group. The two groups were compared for intraoperative parameters, pain score, range of motion of the shoulder joint, shoulder joint function and quality of life (QoL) at pre-operation, 3 and 6 months postoperatively and the final follow-up visit. RESULTS: The width of supraspinatus tendon tear did not exceed 3 cm and did not retract beyond the glenoid in among patients. There was no statistical difference of preoperative data between two groups, including age, course of disease, positive Jobe test, positive Bear-hug test, positive Lift-off test, Patte stage, longitudinal tear and pain severity (P > 0.05). Compared to preoperative levels, the severity of pain, ASES scores and EQ-5D-3L scores were significantly lower at 3 and 6 months postoperatively and the final position (P < 0.05). However, there was no statistical difference in pain severity, ASES scores and EQ-5D-3L scores between repair group and non-repair group (P > 0.05). Similarly, compared to preoperative levels, the range of motion of shoulder joint was significantly improved after operation, including internal rotation, external rotation, forward flexion and elevation (P < 0.05). However, there was no statistical difference in range of motion of shoulder joint between repair group and non-repair group (P > 0.05). CONCLUSION: Operative treatment can effectively lessen severity of pain in the patients, improve shoulder joint function, increase the range of motion of the shoulder joint and enhance the QoL in treating anterosuperior rotator cuff injury. However, repair of subscapularis brings no benefit compared to debridement in treating supraspinatus tendon tear combined with Lafosse I subscapularis injury.

Sleep deprivation and adrenalectomy lead to enhanced innate escape response to visual looming stimuli.

Optimal selections of innate behaviors that enable animals to adapt to particular conditions, whether environmental or internal, remain poorly understood. We report that mice under acute (8 h) sleep deprivation had an enhanced innate escape response and upregulation of c-fos expression in multiple brain areas that regulate wakefulness. By comparison, adrenalectomized mice under the same sleep deprivation condition displayed an even more exaggerated escape response and these wake-regulating brain areas were even more active. This suggests that acute sleep deprivation enhances innate escape response, possibly by altering wake state without causing significant anxiety. We also report that the hypothalamic-pituitary-adrenal axis feedback under sleep deprivation prevents an exaggerated escape response by modulating wake-regulating brain areas. Taken together, our findings suggest that animals prioritize escape response over sleep, as the need of both behaviors simultaneously increase. We also provide an insight into the neural mechanisms underlying the interaction between sleep and innate escape response.

Association of magnesium consumption with type 2 diabetes and glucose metabolism: A systematic review and pooled study with trial sequential analysis.

Prevention of type 2 diabetes (T2D) with diet or diet supplementation is challenging. This article aims to draw conclusive associations between magnesium intake and T2D incidence and evaluate the effect of magnesium supplementation on glucose metabolism. Databases were searched for related articles from inception to May 15, 2019. Prospective cohort studies investigating the relevant relationship as well as randomized controlled trials (RCTs) assessing the effect of magnesium supplementation were eligible. We conducted trial sequential analysis (TSA) to prove the sufficiency of the current evidence. Twenty-six publications involving 35 cohorts were included in the analysis. Compared to the lowest magnesium intake, the highest level was associated with a 22% lower risk for T2D; the risk was reduced by 6% for each 100 mg increment in daily magnesium intake. Additional analysis of 26 RCTs (1168 participants) was performed, revealing that magnesium supplementation significantly reduced the fasting plasma glucose (FPG) level (SMD, -0.32 [95% CI, -0.59 to -0.05], 2-hour oral glucose tolerance test (2-h OGTT) result (SMD, -0.30 [-0.58 to -0.02]), fasting insulin level (SMD, -0.17 [-0.30 to -0.04]), homeostatic model assessment-insulin resistance (HOMA-IR) score (SMD, -0.41 [-0.71 to -0.11]), triglyceride (TG) level, systolic blood pressure (SBP) and diastolic blood pressure (DBP). TSA showed an inverse association, with most benefits of magnesium supplementation on glucose metabolism being stable. In conclusion, magnesium intake has an inverse dose-response association with T2D incidence, and supplementation appears to be advisable in terms of glucose parameters in T2D/high-risk individuals.

Erectile Dysfunction Predicts Cardiovascular Events as an Independent Risk Factor: A Systematic Review and Meta-Analysis.

INTRODUCTION: Previous studies demonstrating that erectile dysfunction (ED) predicts the risk of further cardiovascular events (CV) events are insufficient to make recommendations for cardiologists, diabetologists, urologists, and more, and the association between CV events and ED degree is unclear. AIM: To assess whether ED was a risk factor for CV events in a comprehensive literature review and meta-analysis. METHODS: PubMed, EMBASE, the Cochrane Library, Medline, and the Web of Science were searched for eligible studies. The protocol for this meta-analysis is available from PROSPERO (CRD42018086138). MAIN OUTCOME MEASURES: The main outcomes included cardiovascular disease (CVD), coronary heart disease (CHD), stroke, and all-cause mortality. Subgroup and sensitivity analyses were conducted to detect potential bias. RESULTS: 25 eligible studies involving 154,794 individuals were included in our meta-analysis. Compared with those of men without ED, the CVD risk of ED patients was significantly increased by 43% (relative risk [RR] =1.43; P < .001), CHD was increased by 59% (RR = 1.59; P < .001), stroke was increased by 34% (RR = 1.34; P < .001), and all-cause mortality was increased by 33% (RR = 1.33; P < .001). Older individuals with ED (≥55 years), those with ED of a shorter duration (<7 years), and those with higher rates of diabetes (≥20%) and smoking (≥40%) were more prone to develop CVD. Additionally, severe ED was proven to predict higher CVD and all-cause mortality risk. The standardized model proposed here can be properly applied for screening early CV events. CLINICAL IMPLICATIONS: The evidence prompts the diligent observation of at-risk men and reinforces the importance of early treatment to prevent CV events. STRENGTHS & LIMITATIONS: Larger sample sizes from recent prospective cohort studies were included to provide more up-to-date, reliable, and comprehensive results. Moreover, the results were robust regarding consistency across sensitivity and subgroup analyses and remained consistent; even pre-excluded retrospective or cross-sectional studies were included. We constructed a standardized model that addresses the study's innovations and implications for the first time. However, not all included studies were randomized controlled trials, which might downgrade this evidence. CONCLUSIONS: Risk of total CVD, CHD, stroke, and all-cause mortality was significantly increased in populations with ED, and severe ED is of particular concern. The evidence suggests the need for diligent observation of at-risk men and reinforces the importance of early treatment to prevent CV events. Zhao B, Hong Z, Wei Y, et al. Erectile Dysfunction Predicts Cardiovascular Events as an Independent Risk Factor: A Systematic Review and Meta-Analysis. J Sex Med 2019;16:1005-1017.

Vaccine-based immunotherapy and related preclinical models for glioma.

Glioma, the most common primary malignant tumor in the central nervous system (CNS), lacks effective treatments, and >60% of cases are glioblastoma (GBM), the most aggressive form. Despite advances in immunotherapy, GBM remains highly resistant. Approaches that target tumor antigens expedite the development of immunotherapies, including personalized tumor-specific vaccines, patient-specific target selection, dendritic cell (DC) vaccines, and chimeric antigen receptor (CAR) and T cell receptor (TCR) T cells. Recent studies show promising results in treating GBM and lower-grade glioma (LGG), fostering hope for future immunotherapy. This review discusses tumor vaccines against glioma, preclinical models in immunological research, and the role of CD4+ T cells in vaccine-induced antitumor immunity. We also summarize clinical approaches, challenges, and future research for creating more effective vaccines.

Tumor-reactive T helper cells in the context of vaccination against glioma.

With the advances in immunogenomics, the majority of tumor-specific antigens were found to be recognized by T helper cells (THCs). This observation led to the development of long epitope vaccines in various cancers. Mechanistically, we are still gaining a deeper understanding of the mode of action of THCs as precision antitumor agonists. Here, we discuss the specific cellular mechanisms of THC functions in glioma immunology and contextualize current advances in anti-glioma vaccination exploiting THCs.